Oral 6.1

Antiproliferative Effects of NDC2 and Its Analogues Against Human Hepatocellular Carcinoma (HepG2) Cell Line

Sau Har Lee1*, Cheng Foh Le2 and Chu Xin Ng1
1School of Biosciences, Taylor’s University, Malaysia
2University of Nottingham Malaysia Campus, Malaysia
Corresponding author:Dr. Sau Har Lee, sauhar.lee@taylors.edu.my
Liver cancer is the second most common cause of mortality from cancer worldwide, with a mortality to incidence ratio as high as 0.95. This is mainly attributed to multidrug resistance developed by liver cancer cells after exposure to conventional chemotherapies. Hence, development of therapeutic peptides as a new chemotherapeutic drug might be a promising approach. NDC2 is an Aurein 1.2-like antibacterial and antitumour peptide that was shown to display minimal cell toxicity. We selected this peptide as the template to design five synthetic analogues (ND1–ND5) to enhance its anticancer potential. Therefore, the purpose of this study is to evaluate the in vitro antiproliferative properties of NDC2 and its analogues against human hepatocellular carcinoma (HepG2) cell line.

Each ND analogue was introduced with multiple residual alterations at specific positions at the C-terminal arm. Its anticancer potentials were predicted using the AntiCP anticancer peptide prediction tool. Subsequently, MTT assay was carried out to investigate the potential cytotoxic properties of NDs against HepG2 cells, up to a concentration of 256μg/ml for 24, 48 and 72 hours.
Based on AntiCP algorithm, an anticancer peptide should exhibit SVM score greater than 1.0. From our analysis, only ND1–ND4 showed SVM scores ranging from 1.43–1.78, indicating their higher potential as anticancer peptides. These findings were supported by MTT results that showed both ND5 and the template NDC2 do not possess antiproliferative activity against HepG2 cells. Contrarily, ND1–ND4 exhibited antiproliferative activity against HepG2 cells with IC50 values ranging from 54–104µg/mL after 24 hours treatment. Among these analogues, ND4 was found to be most potent against HepG2 cells, with IC50 value of 54.811±3.403µg/mL. Our findings also showed that there was no significant time-dependent effects for each ND on HepG2 cells.
The four ND1–ND4 analogues exhibited antiproliferative activity against HepG2 cells, thus could represent as promising candidates for treatment against liver cancer. Hence, the anticancer mechanisms of the ND analogues should be further studied.
Keywords: Anticancer peptides (ACPs), Drug Discovery, liver cancer, HepG2, cancer therapy

Oral 6.2

The detection efficacy of anti-MUC1 antibody-based iron oxide nanoparticle on 3D MCF-7 spheroid by Prussian blue and Magnetic resonance imaging

Pegah Moradi Khaniabadi1*, Daryoush Shahbazi-Gahrouei2, Muhammad Asif3, Amin Malik Shah4 and Bita Moradi Khaniabadi2

1School of Physics, University of Science, Malaysia, Malaysia
2Isfahan University of Medical Sciences, Iran
3Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Pakistan
4Department of Pharmaceutical Technology, School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia

Corresponding author: Pegah Moradi Khaniabadi, pegah@usm.my


The United States breast cancer statistics estimated about 266,120 new cases of breast tumour to be diagnosed amongst women in 2018. The noninvasive method of detection in early stages, may help to increase the survival rate of these patients. This study aimed to evaluate the application of anti-MUC1 antibody-based iron oxide nanoparticle (SPION-C595) as molecular imaging probe for breast cancer (MCF-7) cell detection using MRI in vivo.


Nine groups of female NRC Nu/Nu mice (n=3/group; 6 to 8 weeks old) were used. MCF-7 cells were injected subcutaneously into both flanks of these nude mice. After two weeks, the mice received intraperitoneal injection of SPION-C595. Before in vivo study, the uptake ability of nanoprobe on three-dimension (3D) macrostructure was exploited through a modified hanging drop method using Prussian blue for MCF-7 cells. The MR imaging features and biodistribution of nanoprobe was also investigated. The iron content was evaluated on liver, kidney, spleen, and tumour using ICP-OES. In order to determine the influence of storage stability, the nanoprobe was stored at 2 to 8 ºC at different defined time points. The ability of binding on MCF-7 cells was investigated using Prussian blue.


The MR images obtained from digested tumor after nanoprobe administration in different time-period revealed enhanced T1 and T2 relaxation time. The relaxation rate for 200 and 100 µgFe/mL was obtained at 8.06 and 3.88, respectively. The storage stability test indicated the influence of storage stability. Moreover, no sedimentation of nanoparticles was observed within two months storage at 2-8 oC. Additionally, the attachment of SPION-C595 on the 3D spheroid of MCF-7 was confirmed using Prussian blue staning. The biodistribution analysis showed that iron content was the highest in the spleen (2.77±0.35 µg Fe/g organ).The MR images obtained from digested tumor after nanoprobe administration in different time-period revealed enhanced T1 and T2 relaxation time. The relaxation rate for 200 and 100 µgFe/mL was obtained at 8.06 and 3.88, respectively. The storage stability test indicated the influence of storage stability. Moreover, no sedimentation of nanoparticles was observed within two months storage at 2-8 oC. Additionally, the attachment of SPION-C595 on the 3D spheroid of MCF-7 was confirmed using Prussian blue staning. The biodistribution analysis showed that iron content was the highest in the spleen (2.77±0.35 µg Fe/g organ).


These results highlighted the feasibility of an in vivo model for detection of breast cancer MUC1 expression. Current research further enhances relaxation times for classification of MUC1 status using clinical specimens.

Keywords: SPION, MR image, 3D MCF-7 spheroid, C595 monoclonal antibody, Hanging drop

Oral 6.3

In vitro and ex vivo anticolorectal cancer effects of ethanolic Psidium guajava (Guava) leaf extract through inhibition of angiogenesis and colony formation

Bronwyn Lok1, AMS Abdul Majid1, 2*, Hussein M. Baharetha1, 3 and Muhammad Asif4

1Department of Pharmacology, School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia
2ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Australia
3College of Medicine and Health Sciences, Hadramout University of Science and Technology, Yemen
4Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Pakistan

Corresponding author: Dr. AMS Abdul Majid, aminmalikshah@usm.my


Psidium guajava (Guava) leaves had been traditionally used as a treatment for various ailments in tropical and sub-tropical countries. As they are rich in phenols, flavonoids, and carotenoids, it is speculated that extracts from guava leaves may possess anti-angiogenic activity, and in turn, contain anticancer activity on colorectal cancer through their inhibition of angiogenesis.


Three extracts of guava leaves, labelled dH2O, EOH, and NH, were produced using distilled water, ethanol, and n-hexane as solvents. The total phenolic content, total flavonoid content, and DPPH radical scavenging assays were performed to investigate their anti-oxidant potential. In order to assess their anti-angiogenic and anti-cancer properties, the rat aortic ring assay, as well as the cell viability assay on the EA.hy926 human endothelial cell line and HCT116 human colon cancer cell line were conducted. Cell migration, tube formation, and colony formation assays were conducted using the dH2O and EOH extracts against EA.hy926 cells. Finally, the effects of the EOH extract on EA.hy926 cell-VEGF expression was investigated using the enzyme-linked immunosorbent assay (ELISA).


The dH2O and EOH extracts exhibited more inhibitory activity against the growth of microvessels from rat aortic rings (76.75 ± 11.10 and 75.67 ± 7.29%), as well as against EA.hy926 (51.73 ± 4.31 and 54.18 ± 9.05%) and HCT116 (51.30 ± 3.05 and 49.09 ± 7.00%) cell viability when compared to the NH extract. The extracts were not cytotoxic towards the two cell lines, which indicated that the extracts express anti-tumoural properties via other pathways. The dH2O and EOH extracts also inhibited angiogenesis (i.e. cell migration and tube formation) and colony formation. Among the three extracts, the EOH extract has the best anti-oxidant activity. After treatment with the EOH extract, the VEGF expression of the EA.hy926 cells was also successfully inhibited (52.21 ± 6.00%).


The EOH guava leaf extract showed promising anti-angiogenic effect in vitro and ex vivo. It can be concluded that the EOH extract has potential in the treatment of colorectal cancer.

Keywords: Angiogenesis, Psidium guajava, Colorecta cancer, Antioxidant acti vity, Vascular endothelal growth factor

Oral 6.4

Functions of TRPM4 and Cytotoxic Effects of the Selective TRPM4 Inhibitor 9-phenanthrol in Diffuse

Kah Keng Wong1*

1University of Science, Malaysia, Malaysia

Corresponding author:Dr. Kah Keng Wong, kahkeng@usm.my


We have previously shown that transient receptor potential cation channel subfamily M member 4 (TRPM4) was overexpressed in activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) significantly associated with poor survival. However, its functions in the disease as well as the potency of its selective inhibitor 9-phenanthrol are unknown.


The biological functions associated with TRPM4 mRNA expression were examined in 15 ABC-DLBCL cases previously gene expression profiled and with known TRPM4 protein status (n=10 TRPM4-negative; n=5 TRPM-positive). Gene Set Enrichment Analysis (GSEA) was conducted in the cases according to the gene sets annotated by Reactome database. The cytotoxicity effects of 9-phenanthrol in three ABC-DLBCL cell lines (SUDHL2, OCI-LY3, OCI-LY10) was tested at six different concentrations (0.01nM, 0.1nM, 1nM, 10nM, 25nM, 50nM) with vehicle-only control according to MTS assay protocols. These were conducted in triplicate at three different time points (24-hour, 48-hour, 72-hour) and three independent experiments were performed.


GSEA results showed that cell cycle gene sets conferred the highest number of gene sets representing 42% (n=21/50) of the top 50 most significantly enriched gene sets ranked according to false discovery rate (FDR; all 50 gene sets had FDR<0.01). These were followed by DNA replication (n=8/50; 16%), RNA processing (n=8/50; 16%), chromosome processing (n=6/50; 12%) and other gene sets (n=7/50; 14%), suggesting the roles of TRPM4 in cell cycle progression and cellular division of ABC-DLBCL. In terms of the cytotoxicity effects of 9-phenanthrol, the resulting GI50 for all ABC-DLBCL cell lines tested ranged from 19nM-41.88nM across the three time points of treatments.


TRPM4 is potentially involved in the cell cycle progression and cellular division of ABC-DLBCL cells, and the TRPM4 inhibitor 9-phenanthrol was potent against the viability of ABC-DLBCL cells at nanomolar concentrations, indicating its therapeutic potential against ABC-DLBCL.

Keywords: TRPM4, 9-phenanthrol, diffuse large B cell lymphoma, Cell Cycle, Gene set enrichment analysis (GSEA)


Oral 7.1

Psychometric Analysis of the newly translated Malaysian version of Diabetes Knowledge Questionnaire by Rasch analysis

Muhammad Qamar1*, Raiz Rasyid M. Iqubal1 and Sohail Ahmad1

1Faculty of Pharmacy, Mahsa University, Malaysia

Corresponding author:Mr. Muhammad Qamar, mqamar18@gmail.com


Diabetes mellitus (DM) has become one of the most significant non communicable and rampant diseases. Patient education is a key element in the management of diabetes in order to improve patient outcomes. For the assessment of diabetes knowledge, validated tool is essential. Therefore, the aim of this study was to translate and assess the psychometric properties of Malay version of Diabetes Knowledge Questionnaire (M-DKQ) among type 2 diabetes patients.


Permission was obtained from respective authors to translate the English version of DKQ into Malay language according to established standard international translation guidelines. In this study 50 adult diabetes patients were recruited from Kedah by convenience sampling method. The data were extracted from the self-administered questionnaires and entered manually in the Ministeps (Winsteps) software for Partial Credit Rasch Model. The item and person reliability, infit/ outfit Z-Standard (ZSTD), infit/outfit Mean Square (MNSQ) and point measure correlation (PTMEA Corr) values were analysed for the reliability analyses and construct validation.


Rasch analysis confirmed that the Malay version of DKQ with a three-point rating scale demonstrated good internal consistency (item reliability=0.86, person reliability=0.66). The output tables of item construct showed that values for infit and outfit MNSQ (0.6 to 1.4), infit and outfit ZSTD (±2), and PTMEA correlation (0.3 to 0.6) were within the acceptable range for all the items except for four items: item number 4, 7, 16, and 20. The newly devised translated questionnaire satisfy the specification of the Rasch Model for reliability (n=24) and construct validity (n=20).


The Malay version of DKQ could reliably measure the knowledge of DM among Malaysian adult diabetics. Four items need to be rephrased in order to validate the complete questionnaire construct by Rasch model.

Keywords: Type 2 diabete mellitus, Realiabilty, Malay Version, Rasch model, DKQ

Oral 7.2

Predictors of Stroke Recurrence in Malaysian Diabetic Population with Different Body Mass Index Classification: The observation from Malaysian National Stroke Registry

Sabariah Noor Harun1*, Siti Maisharah Sheikh Ghadzi1, Nur Ezzati Abidin1, Balamurugan Tangiisuran1, Hadzliana Zainal1, Irene Looi2, khairul Azmi Ibrahim3, Norsima Nazifah Sidek3, Loo K. Wei4, Keng Yee Lee5 and Zariah Abdul Aziz3

1School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia
2Clinical Research Center, Hospital Seberang Jaya, Malaysia
3Clinical Research Center, Hospital Sultanah Nur Zahirah, Malaysia
4Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, Malaysia
5Clinical Research Centre, Malaysia

Corresponding author:Dr. Sabariah Noor Harun, fussilat4130@gmail.com


Body mass index and diabetes mellitus are the most commonly reported strong independent risk factors for having a stroke and its recurrence. However, does the predictor of stroke recurrence among diabetic patients who have normal body weight different from those who are overweight or obese, need to be investigated and supports the importance of this study.


The data from 4622 patients with T2DM was obtained from the Malaysian National Stroke Registry. The subjects were classified as having normal body weight (n=1520), overweight (n=1034) and obese (n=2068) with body mass index (BMI) of 18-24, 24-30, and > 30, respectively. Logistic regression analysis was applied to assess the association between the factors and the risk of having a recurrent stroke. The data were analysed using SPSS version 22.


Having an ischemic heart disease (IHD) increase the odds of having a recurrent stroke in diabetic patients who are obese as well as with normal body weight with (OR=2.84; 95%CI [1.55,5.21], P=0.001) and OR= 2.29; CI 95% [1.24-4.25], P=0.001 respectively. Nevertheless, ethnicity other than Malay, Chinese and India was the significant factor reducing the odds of having a recurrent stroke in diabetic Malaysian population who were obese (OR= 0.51; CI 95% [0.28-0.91], P=0.02) and normal body weight (OR= 0.47; CI 95% [0.26-0.84], P=0.01). Active smoking was the independent risk factor of recurrent stroke in an obese diabetic patient (OR= 2.18; 95%CI [1.21-3.9], P=0.01) whereas experiencing monoparesis during the first stroke event increase the odds of having a recurrent stroke in an overweight diabetic patient with OR= 6.40; 95% CI [1.76-23.3], P=0.01.


IHD was a significant modifiable predictor of recurrent stroke in obese and normal weight diabetic Malaysian population. The extent of optimising IHD management in influencing the risk of future stroke attack may need to be explored.

Keywords: Recurrent stroke, Type 2 diabete mellitus, Body Weight, Risk factors, Malaysian

Oral 7.3

Pharmacometrics Application in the Time-To-Event
Modelling of Recurrent Stroke among Patients with
Type 2 Diabetes Mellitus

Siti Maisharah Sheikh Ghadzi1*, Sabariah Noor Harun1, Nur Ezzati Abidin1, Balamurugan Tangiisuran1, Hadzliana Zainal1, Irene Loo2, Khairul Azmi Ibrahim3, Norsima Nazifah Sidek3, Keat Wei Looi4, Keng Yee Lee5 and Zariah Abdul Aziz5
1School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia
2Clinical Research Center, Hospital Seberang Jaya, 
3Clinical Research Center, Hospital Sultanah Nur Zahirah, Malaysia
4Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Kampar Campus, 
5National Clinical Research Center

Corresponding author: 
Dr. Siti Maisharah Sheikh Ghadzi, maisharah@usm.my


Pharmacometrics approach is a better alternative than traditional methods to perform the time-to-event analysis, as it allows parametric quantification as well as taking into account censoring and time components into the analysis. The objective of this study was to develop a time-to-event (TTE) model in patients with type 2 diabetes mellitus (T2DM) using pharmacometrics modelling.


The data from 4622 patients with T2DM were obtained from the Malaysian National Stroke Registry and were analyzed using NONMEM. The maximum time of follow-up years was 10.8 years. TTE models of exponential, Gompertz and Weilbull were fitted to the data for the base model. The event was described as having a recurrent stroke after the first attack. The best base model was chosen for univariate analysis of covariates, for examples demographics, etc. The likelihood ratio test with a significance level (α) of 5% was used for the analysis. The final model was chosen based on the lowest objective function value, graphical and numerical evaluation as well as the scientific plausibility.


Out of 4622 subjects, 227 (4.91%) developed a recurrent stroke within the maximum 10.8 years follow-up. The best base model was Gompertz with the baseline hazard for the Gompertz distribution was 0.0213 year-1. The hazard of developing recurrent stroke from the previous attack decreased with time with a half-life of 2.06 years, CI [0.83, 1.17]). Ischemic heart disease and hyperlipidemia increased the risk of recurrent stroke (HR, 2.06; 95% CI [1.55-2.75] and HR, 1.82; 95% CI [1.41-2.35], respectively).


Pharmacometrics analysis is a useful approach in performing the survival analysis. IHD and hyperlipidemia were significantly increased the risk of recurrent stroke after the first attack. The results in this study may add into the knowledge related to this issue, thus may help to guide the management for the prevention of recurrent stroke in T2DM patients.

Keywords: pharmacometrics, Recurrent stroke, type 2 diabetes mellitus, covariates, Time-to-event

Oral 7.4

Hepatoprotection by probiotics in vivo: a systematic review and meta-analysis

Faezah Sabirin1, 2, 3*, Siong Meng Lim1, 2, Chin Fen Neoh1, 2 and Kalavathy Ramasamy1, 2*

1Faculty of Pharmacy, University Technology Mara, Malaysia
2Collaborative Drug Discovery Research Group, Research Unit of Pharmaceutical and Life Sciences, University Technology Mara, Malaysia
3Faculty of Dentistry, Universiti Teknologi MARA, Malaysia

Corresponding authors: DVM. Faezah Sabirin, drfaezah@gmail.com and
Dr. Kalavathy Ramasamy,  kalav922@gmail.com


The severity of nonalcoholic fatty liver disease (NAFLD) has been found to be associated with gut dysbiosis. Probiotics, which are beneficial in maintaining a healthy gut, may be useful in delaying development of NAFLD. This study was undertaken to systematically review and analyse the impact of evidence pertaining to probiotic supplementation in NAFLD in vivo.


Literature search was conducted between October 2017 – May 2018 using Cochrane, PubMed/ MEDLINE, Embase, Springer and Web of Science. Article identification and data extraction were performed by four reviewers based on inclusion and exclusion criteria. Risk of bias was assessed using SYRCLE tool. Meta-analysis was performed using RevMan 5.3. The primary outcomes included severity of liver histopathology [i.e. total NAFLD activity score (NAS)] and serum alanine aminotransferase (ALT). The secondary outcomes included hepatic lipid and triglyceride, as well as serum triglyceride, HDL and LDL cholesterol. Mean differences (MD) or standard MD (SMD) between groups were analysed using Random-Effect Model. Statistical heterogeneity was assessed using I2 test.


Twenty-eight studies were included in the systematic review whilst only 9 were selected for subsequent meta-analysis. The shortlisted literature was predominantly presented with low or unclear risk of bias. When compared to control, the total NAS was significantly lower in probiotic group (MD=-1.81; 95% CI=-2.37, -1.24, p<0.00001). The heterogeneity was moderate but insignificant (I2=55%, p=0.05). Significant reduction in ALT was noted in probiotic group (MD=-0.99; 95% CI=-1.55, -0.43, p=0.0005). The heterogeneity was, however, substantial (I2=70%, p<0.0001) when compared to control. The significant reduction in total NAS was accompanied by significantly lower hepatic lipid (p<0.00001) and triglyceride (p<0.0001). Nevertheless, no significant changes were noted in other serum parameters.


Probiotic supplementation was associated with significant reduction in total NAS and ALT. The present findings strongly implied the hepatoprotective potential of proboitics.

Keywords: Probiotics, NAFLD (non alcoholic fatty liver disease), total NAFLD activity score, ALT, Hepatic lipid, hepatic triglyceride, Dysbiosis

Oral 7.5

Vasorelaxant study of standardized extract of Pericarpium Citrus reticulatae

Chu Shan Tan1 and Mun Fei Yam1*

1School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia

Corresponding author:Dr. Mun Fei Yam, yammunfei@yahoo.com


Pericarpium Citrus reticulatae (Chen pi in Chinese) was widely used as an important ingredient in the prescription of Traditional Chinese Medicine (TCM) to treat hypertension and is one of the famous ingredients officially listed in Chinese Pharmacopoeia. Since Chen pi has been included in major TCM formulations to treat hypertension, it is a correlated and justifiable expectation that Chen pi possesses vasorelaxant properties.


This study is designed to investigate the vasorelaxant effect of Chen pi standardized extracts using Sprague Dawley rat isolated thoracic aortic ring assay.


Among the different solvent extracts, water extract of Chen pi (CRW) exhibited the strongest vasorelaxant activity. CRW caused the relaxation of the phenylephrine pre-contracted aortic rings in the presence and absence of endothelium as well as in potassium chloride pre-contracted endothelium-intact aortic ring. The incubation of propranolol (β-adrenergic receptor blocker), atropine (muscarinic receptor blocker), Nω-nitro-L-arginine methyl ester (NO synthase inhibitor), ODQ (sGC inhibitor), indomethacin (COX inhibitor), 4-aminopyridine (KV blocker), barium chloride (Kir blocker), and glibenclamide (KATP blocker) significantly reduced the vasorelaxant effects of CRW. CRW was also found to be active in reducing calcium releases from the sarcoplasmic reticulum and suppressing the voltage-operated calcium channels.


The vasorelaxant effect of CRW on rat aorta involves NO/sGC, calcium and potassium channels, muscarinic and β-adrenergic receptors.

Keywords: Pericarpium Citrus reticulatae, NO/sGC pathway, Potassium and calcium channels, Traditional Chinese Medicine, Vasorelaxation

Oral 7.6

Lignosus rhinocerotis water-soluble sclerotial extract relaxes rat isolated aortae.

Kayatri Govindaraju1, Mei Kee Lee1, Kang Nee Ting1*, Chon Seng Tan2, Szu Ting Ng2, Hwei-San Loh1, Sue Mian Then1 and Suresh K. Mohankumar1

1Department of Biomedical Sciences, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia, University of Nottingham Malaysia Campus, Malaysia
2LiGNO Biotech Sdn Bhd, Malaysia

Corresponding author:Prof. Kang Nee Ting, kang-nee.ting@nottingham.edu.my


Lignosus rhinocerotis (Cooke) Ryvarden commonly known as Tiger Milk Mushroom is a popular traditional medicinal mushroom used in Southeast Asia to treat many conditions including asthma, cough and cancer. Many other edible mushrooms such as Cordycep sinensis have reported to exhibit antihypertensive effects. The study aims to investigate the vascular effects of L. rhinocerotis in rat isolated aortae.


Organ bath setup was used to study the effects of L. rhinocerotis cold water extract (CWE) in aortic rings isolated from (8-10) weeks old male Sprague Dawley rats. All the aortic rings were pre-contracted with phenylephrine prior to the construction of concentration-response curve to the extract. The role of endothelium and muscarinic receptor–mediated relaxation of the smooth muscle protocols was performed. Calcium channel inhibitors, 1-[2-(4-Methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole hydrochloride (SKF96365) and nifedipine, were used as positive controls to confirm the role of external calcium in eliciting contractions induced by phenylephrine in this preparation.


Results showed that CWE significantly relaxed the pre-contracted aorta (Emax: 97.70 ± 5.21%). Removal of endothelium or blockade of muscarinic receptor did not affect CWE-induced vasorelaxation. SKF96365 and nifedipine markedly attenuated phenylephrine-induced contractions showing the crucial role of external calcium.


This is the first study to report the vasorelaxation effects of L. rhinocerotis in rat isolated aorta. These effects are endothelium-independent and likely to be via blockage of calcium channels.

Keywords: Lignosus rhinocerotis, medicinal mushroom, vascular smooth muscle, Vasorelaxation, organ bath


Oral 8.1

STIM and ORAI Genes, Interactions with Transcription Factors, Differential Gene Expression and Co-expression Analysis on Breast Invasive Carcinoma Dataset

Ruzianisra Mohamed1*, Riccha Sethi2, Mohamed Hamed3 and Volkhard Helms2

1Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, 42300 Bandar Puncak Alam,, Universiti Teknologi MARA Puncak Alam, Malaysia
2Center for Bioinformatics, Building E2 1, P.O. Box 151150, 66041, Saarland University, Germany
3Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Ernst-Heydemann-Straße 8, 18057, Universitätsmedizin Rostock, Germany

Corresponding author:Dr. Ruzianisra Mohamed, ruzianisra@puncakalam.uitm.edu.my


Store-operated calcium (Ca2+) entry (SOCE) is ubiquitous mechanism for Ca2+ entry in eukaryotic cells, which regulates diverse cellular functions. SOCE is achieved primarily by the gating of the plasma membrane (PM)-localized-channel, ORAI, by the ER-localized Ca2+-sensing protein, STIM. The discovery of transcription factor binding site (TFBS) motifs in specific locations on the STIM and ORAI promoters remains elusive. Moreover, the knowledge of the defects of STIM and ORAI genes expression and/or function linked to disease such as breast cancer is still obscured.


Here, the HOCOMOCO and EPDnew databases were used to obtain a set of position weight matrix (PWM) and promoter sequences of STIM and ORAI, respectively, and mapped the possible binding motif proteins using the FIMO tool. The results were then mapped with the set of transcription factors (TFs) targeting STIM and ORAI gene which were retrieved from the CheA database.


Ten predictive interactions were used between transcription factors bound to promoter regions of STIM and ORAI genes based on predictions using the STRING, prePPI, and mentha databases. Then, the collection of 63 TFs was used as gene of interest for co-expression and differential expression analysis on breast invasive carcinoma (BRCA) dataset. There, ORAI genes were found to be up-regulated, in contrast with STIM1 and STIM2 which were down-regulated.


Unveiling the predicted transcription factors bound to the promoter regions of STIM and ORAI genes, the regulations of these genes and differential networks properties may suggest putative interactions for experimental studies and allows us to gain knowledge in relation to breast cancer.

Keywords: STIM, Orai, Breast invasive carcinoma (BRCA), promoters, Transcription Factors

Oral 8.2

The Development of ReFOLDa a New Rapid Iterative Protein Refinement Protocol Guided by State-of-the-art Quality Assessment Programs for the Selection of Optimal Refined Model.

Ahmad N. Shuid1*

1University of Science, Malaysia, Malaysia

Corresponding author: Dr. Fatimah Hashim, fatimah.h@umt.edu.my


Extraction of relevant information on structures and functions of proteins have been dependent on numerous potential computer-based protein modelling programs that are resourceful and time efficient. However, progress on refining the predicted models has been slow. Most of the computer-based refinement programs had generally failed to improve over the starting protein model consistently. Thus enhancing the accuracy of starting models continues to be one of the crucial and challenging problems in structural bioinformatics as the development and exploration of new drugs are highly dependent on model accuracy. Previously we have developed state of the art hybrid refinement protocol known as ReFOLD server (http://www.reading.ac.uk/bioinf/ReFOLD/) for protein refinement. With ReFOLD success in the recent CASP12 experiment, we aim to design another variant of ReFOLD refinement programs that can run on any platform with minimal computational power.


In this experiment we have developed another variant of ReFOLD server (ReFOLDa) that uses i3Drefine to improve the structure of the starting protein models. ReFOLDa protocol was also integrated with Method 42 that select the best predicted refined models based on the trajectory of the predicted QA scores (ModFOLD5_single) for the first seventh iterations. The performance of ReFOLDa in comparison to the ReFOLD was then tested using the targets from the CAPS12 experiment. TMscore was used to calculate the observed scores for the generated refined models and R statistical software was used to study the significance of the observed differences between ReFOLD and ReFOLDa.


The paired-sample t-tests and Wilcoxon-ranked sum-tests revealed that ReFOLDa (Mean = 0.3962) protocol performed better than ReFOLD (Mean = 0.3839) for refining the targets from the refinement category and was on par with ReFOLD for refining the targets from the tertiary structure prediction category of the CASP12 experiment.

Keywords: Refold, ReFOLDa, protein refinement, drug design, structural bioinformatics

Oral 8.3

The Molecular Docking of Substituted Schiff Bases Derived from S-Benzyldithiocarbazate as Potential Anticancer Agents

Fiona N. How1*, Zalikha Ibrahim1 and Nur Insyirah Zulkifli1

1Department of Chemistry, International Islamic University Malaysia, Malaysia

Corresponding author: Dr. Fiona N. How, howfiona@gmail.com


Breast cancer is one of the lethal diseases worldwide. According to the Malaysia National Cancer Registry Report (MNCR 2007-2011), 13.2% from 103,407 new cases of cancer detected throughout Malaysia was breast cancer. The current treatments available are chemotherapy and hormone therapy using tamoxifen. However, it causes some side effects, which includes extreme fatigue, loss appetite, and depression. Therefore, there is a need for more targeted and less side-effect anti-cancer drug. Substituted Schiff bases derived from S-benzyldithiocarbazate are well known for their profound anticancer activity. However, there is no relationship to correlate the structural variation with their anticancer activity. This study served as the very first premier work to uncover the structure-activity relationship of the substituted Schiff bases derived from S-benzyldithiocarbazate.


This research sought to predict the binding affinity and molecular interactions which are responsible for the anticancer activity of the Schiff bases towards estrogen receptor alpha (ERα) using molecular docking study. Ten substituted Schiff bases were extracted from previous reported literature and one standard drug, tamoxifen were docked towards onto the crystallised structure of ERα (PDB ID: 3ERT).


All the ten substituted Schiff bases and tamoxifen exhibited good binding affinity towards the receptor ERα ranging from -9.9 to -3.8 kcal/mol. Comparative analysis on the binding interactions of the docked complexes showed that the Schiff bases have different binding interactions with the receptor compared to the standard drug, tamoxifen. Among the Schiff bases, it was observed that the Schiff bases with 5-chloroisatin, 5-fluoroisatin and 5-bromoisatin showed the best binding affinity towards ERα with -8.4, -8.2, -8.1 kcal/mol respectively, exerted good IC50 values ranging from 6.40 to 38.60 µg/mL which was lower than tamoxifen (10.03 µg/mL). The good binding affinities were achieved due to the presence of hydrogen bonding and hydrophobic interactions between the Schiff bases and amino acid residues of ERα. The results showed that the presence of aromatic rings, halogen, and nitrogen, functional groups in the chain of substituted Schiff bases greatly affect the binding affinity.


This study concluded that there is a relationship between the structural differences of the Schiff bases and their anti-cancer activities It is expected that this relationship can be utilized for the development of anticancer drugs with improved selectivity, effectiveness and efficacy.

Keywords: breast cancer, Substituted dithiocarbazate derivatives, binding affinity, Estrogen Receptor alpha, molecular docking

Oral 8.4

Molecular Docking Studies for the Identification of Novel APOBEC3B Inhibitors using Different Docking Routines

Nor A. Jusril1, 2, Shahrul I. Abu Bakar1, 2, Mohd I. Adenan1 and Ng K. Wen1, 2, 3*

1Faculty of Applied Sciences, Universiti Teknologi Mara, Malaysia
2Atta-ur-Rahman Institute for Natural Product Discovey, Universiti Teknologi MARA, Malaysia
3Centre of Foundation Studies, Universiti Teknologi MARA, Malaysia

Corresponding author: Dr. Ng K. Wen, kwokwen.ng@gmail.com


Overexpression of the enzyme APOBEC3B (A3B) DNA cytosine deaminase is an inciting factor for tumor progression across a range of cancer types. Dysregulation of A3B results in C-to-T or C-to-G mutations during cellular replication. Evidence of A3B association with proliferation related to oncogenes, replication stress, and drug sensitivity of cancer cells are well-documented. Consequently, therapeutic interventions using small molecules in the modulation of A3B could provide opportunities for cancer prevention or treatment. The present study seeks to narrow down prospective chemical scaffolds that could interact with the A3B enzyme, using computer-aided methods.


Molecular docking and virtual screening of 2000 compounds of diverse structures were performed using an open source modelling simulation software programs, AutoDock, Vina, and Gold. The molecular models of each compound were constructed and optimized prior to the docking simulations against A3B (PDB ID: 5TD5). Docking parameters, such as grid dimension, run repetition, and types of algorithms used, were ameliorated to ensure accuracy in the virtual screening. A combination of scoring, minimization, and redocking using the software programs on the drug libraries set was employed to select active compounds through rapid gradient-optimization conformational search. The results were then compared to the outcome from software programs, which ranked the active compounds using rapid Lamarckian genetic algorithm search method and empirical free energy force field.Molecular docking and virtual screening of 2000 compounds of diverse structures were performed using an open source modelling simulation software programs, AutoDock, Vina, and Gold. The molecular models of each compound were constructed and optimized prior to the docking simulations against A3B (PDB ID: 5TD5). Docking parameters, such as grid dimension, run repetition, and types of algorithms used, were ameliorated to ensure accuracy in the virtual screening. A combination of scoring, minimization, and redocking using the software programs on the drug libraries set was employed to select active compounds through rapid gradient-optimization conformational search. The results were then compared to the outcome from software programs, which ranked the active compounds using rapid Lamarckian genetic algorithm search method and empirical free energy force field.Molecular docking and virtual screening of 2000 compounds of diverse structures were performed using an open source modelling simulation software programs, AutoDock, Vina, and Gold. The molecular models of each compound were constructed and optimized prior to the docking simulations against A3B (PDB ID: 5TD5). Docking parameters, such as grid dimension, run repetition, and types of algorithms used, were ameliorated to ensure accuracy in the virtual screening. A combination of scoring, minimization, and redocking using the software programs on the drug libraries set was employed to select active compounds through rapid gradient-optimization conformational search. The results were then compared to the outcome from software programs, which ranked the active compounds using rapid Lamarckian genetic algorithm search method and empirical free energy force field.


Seven hit compounds with high scoring from docking the software which contain fewer than five rigid and rotatable bonds, having tendency to be planar, with one or less chiral centres and pharmacologically desirable features, were identified. These compounds were ranked highest among the 2000 structures in the simulation scoring and have an indistinguishable binding energy profile with A3B.Seven hit compounds with high scoring from docking the software which contain fewer than five rigid and rotatable bonds, having tendency to be planar, with one or less chiral centres and pharmacologically desirable features, were identified. These compounds were ranked highest among the 2000 structures in the simulation scoring and have an indistinguishable binding energy profile with A3B.


Here, seven promising small inhibitor molecules of A3B enzymatic activities are reported. The findings from this project should significantly shorten the time in the designing the first-in-class novel molecules against the A3B, as well as for subsequent in vitro and in vivo studies.

Keywords: molecular simulation and docking, Cancer, inhibitors, Software, APOBEC3B

Oral 8.5

Chemical Constituents and Antimicrobial Properties of the Bark of Phyllanthus acidus (L.) Skeels

Siow-Ping Tan1*, Qian-Yu Lim1, Hui-Yin Tan1 and Mohd Azlan Nafiah2

1Tunku Abdul Rahman University College, Malaysia
2Sultan Idris University of Education, Malaysia

Corresponding author:Dr. Siow-Ping Tan, tansp@tarc.edu.my

Phytochemical investigation of the bark of Phyllanthus acidus (L.) Skeels led to the isolation of two chemical entities, namely meso-hydrobenzoin (1), 2-ethylhexyl isonicotinate (2) and squalene (3) via chromatography methods. The structures of these compounds were characterized and identified by spectral analyses, such as NMR, IR and GCMS. To the best of our knowledge, compounds 1 and 2 were isolated from this plant for the first time. The bioassay experiment by disc diffusion method indicated that the various crude extracts of the bark at concentration of 20 mg/mL exhibited positive antimicrobial results against Staphylococcus aureus, Klebsiella pneumoniae with disc inhibition zone range of 6.7–9.0 mm; and Escherichia coli with disc inhibition zone range of 5.0–6.0 mm; but inactive against Pseudomonas aeruginosa. The results in the present study suggest that the bark of P. acidus can be used in treating diseases caused by the tested organisms.

Keywords: Phyllanthus acidus (L.) skeels, hydrobenzoin, Isonicotinate, Antimicrobial activity, phytochemistry

Oral 8.6

Structural Basis for Dengue Virus Antibody Dependent Maturation

Jan K. Marzinek1 and Peter J. Bond1*

1Bioinformatics Institute (A*STAR), Singapore

Corresponding author:Dr. Peter J. Bond, peterjb@bii.a-star.edu.sg


Dengue virus (DENV) is responsible for millions of infections a year around the world. DENV is composed of an RNA genome complexed with capsid (C) proteins, which are surrounded by envelope (E) and membrane (M) proteins embedded within a lipid bilayer. In nascent viral particles, the pre-membrane (prM) protein caps the fusion loop of the E protein, making it non-fusogenic. During maturation, cleavage of prM into the M protein and release of pr leads to a conformational change in the E protein that makes it fusion-competent. Interestingly, DENV is known to be released from cells under different states of maturation. Fully immature DENV (immDENV) is non-infectious. However, its infectivity can be enhanced when DENV is targeted by host anti-prM antibodies. The molecular basis for this antibody-dependent enhancement has until recently been unknown.


In this work, cryo-electron microscopy (cryo-EM) structures of the immDENV:anti-prM complex at acidic and neutral pH conditions mimicking the endosomal and extracellular environments respectively were analyzed via integrative modeling and simulation approaches.


At acidic pH, an intermediate structure of the DENV maturation pathway has been solved with fewer antibodies bound in comparison to neutral pH. Based on previously developed multiscale models of the DENV particle, we employed sets of targeted molecular dynamics (TMD) simulations in order to trigger the maturation transition at low pH. Hydrogen-deuterium exchange mass spectroscopy and Elisa measurements confirmed that the affinity of the antibody:pr complexes are stronger than those of the pr:E complexes, and the TMD simulations revealed dislodgement of antibody:pr from the E protein surface during the conformational transition due to steric clashes.


Here, we provide the detailed molecular mechanism by which anti-prM antibodies enhance maturation of DENV in the acidic endosomal environment, leading to exposure of the E protein fusion loops for subsequent endosomal membrane binding and fusion.

Keywords: Dengue virus maturation, cryo-electron microscopy, antibody, PRM, Molecular dynamic simulations

Oral 8.7

Influence of Polymorphisms in Chemokine Receptor-5 (Ccr5) and Ccr2 On Susceptibility to HIV, Viral Load And CD4 Count With Anti-Retroviral Therapy

Irma Izani Mohamad Isa1 and Suhaili Abu bakar1*

1Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, Malaysia

Corresponding author:Dr. Suhaili Abu bakar, suhaili_ab@upm.edu.my


Genetic variation of the host can influence susceptibility and pathogenesis of some diseases including HIV/AIDS. CCR5 is a HIV co-receptor used by the virus for entry to the host cells. Certain polymorphisms in CCR5 and CCR2 can provide protection against HIV infection and lead to slower rate of progression to AIDS. This study aimed to investigate the CCR5-Δ32, CCR5-R223Q and CCR2-V64I mutations with susceptibility to HIV, viral load suppression and CD4 recovery following highly active anti-retroviral therapy (HAART) in Malaysian population.


Ethical approval was obtained from the ethics committees of medical research (MREC) and UPM. 175 HIV-infected and 150 healthy subjects of Malay, Chinese and Indian ethnics were recruited from out-patient clinics of three selected hospitals and university areas respectively. CCR5-Δ32 was genotyped by polymerase chain reaction (PCR) while CCR5-R223Q and CCR2-V64I were identified using PCR-restriction fragment length polymorphism (RFLP). CD4 count and viral load were extracted from medical record and followed for up to 18-24 months after the initiation of HAART. T-test/one-way ANOVA and chi-squared test were used in CD4 and viral load analyses respectively.


CCR5-Δ32, CCR5-R223Q and CCR2-V62I were not significantly different in healthy as compared to HIV-infected subjects, indicating the absence of protective effect of these polymorphism to HIV infection. Both CD4 recovery and viral load suppression were also not associated with CCR5-Δ32, CCR5-R223Q and CCR2-V62I.


CCR5-Δ32, CCR5-R223Q and CCR2-V62I have no impact on HIV susceptibility, CD4 recovery and viral load in Malaysian population. Further studies are needed to identify other host genetic variants that can explain variation in individuals’ response to HAART towards precision medicine for the treatment of HIV infection

Keywords: CCR5, CCR2, HIV, CD4, Viral Load

Oral 8.8

Effect of Annona squamosa extract combined with permetrin 5% on scabies lesion

Renni Yuniati1*, Prasetyowati Subchan1, Irnawanti Irnawanti1 and Falah Faniyah1

1Department of Dermatology and Venereology, Diponegoro University, Indonesia

Corresponding author: MD, PhD. Renni Yuniati, renniyuniati@yahoo.com


Scabies is one of the top six dermatology disease in the world as stated by World Health Organization and one of the top three dermatology disease in Indonesia. Its treatment comprises of many agents. Nowadays, back-to-nature concept using traditional medicine is the preferable choice for scabies. This study aimed to investigate the effect of Annona squamosal leaf extract in combination with permetrin 5% ointment on scabies lesion.


This was a quasi experimental study with pre- and post-test design conducted in one of Islamic Boarding School in Pati regency, Central Java Province, Indonesia. This study was performed on 24 eligible subjects divided into six groups: control group who received permetrin 5% only, and five treatment groups who received permetrin 5% and Annona squamosal leaf extract ointment in five different concentrations (0.1%, 0.5%, 1%, 5%, and 10% for subgroup T1, T2, T3, T4, and T5, respectively). The preparations were applied once a week for three weeks.


There were significant delta scabies lesions difference between control and subgroup T1 (p=0.021), control and subgroup T2 (p=0.021), control and subgroup T3 (p=0.020), control and subgroup T4 (p=0.021), and control and subgroup T5 (p=0.021).


Annona squamosa leaf essential oil based ointment which used in combination with permetrin 5% could increase scabies treatment effectiveness.

Keywords: Annona squamosa, Annona squamosa leaf extract ointment, Scabies, Traditional medicine (TM), scabies adjuvan therapy


Oral 9.1

HTR1A-RS6295 polymorphism and selective serotonin reuptake inhibitor treatment outcome in major depressive disorder patients

Ibrahim M. Badamasi1*, Johnson Stanslas2, Munn Sann Lye1, Khozirah Shaari3 and Normala Ibrahim1

1Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia
2Putra Malaysia University, Malaysia
3Institute of Bioscience, University Putra Malaysia, Malaysia

Corresponding author:Dr. Ibrahim M. Badamasi, badamasiibrahimmohammed@gmail.com


Production of serotonin is influenced by serotonin-1A receptor (5HTR1A). RS6295-HTR1A is a promoter region polymorphism in the HTR1A gene, which is characterised by cytosine(C) substitution with guanine (G), which modulates serotonergic neurotransmission. The current study was aimed at determining the association between HTR1A-RS6295 gene polymorphism with SSRI treatment outcome.


Consecutive sampling was adopted for recruiting consenting multiethnic Malaysian patients in four tertiary hospitals, namely Hospital Serdang, Hospital Kajang, Hospital Putrajaya and Hospital Kuala Lumpur. Montgomery Asberg Depression Rating Scale-self Rated (MADRS-S) was used in determining efficacy of SSRI following 6 weeks of treatment. Adverse effects (AEs) were assessed using Patient Rated Inventory of Side Effect (PRISE) at the 6th week of treatment. Statistical evaluation of association between genotypes of HTR1A-RS6295, obtained through sequencing of PCR products, with phenotypes of efficacy and AEs, before and after adjustment with covariates was done.


There were 314 patients, 211 (67%) were females and 154 (49%) were Malays. In this study, 73.4%, 70.7% and 71.7% of the patients were observed to have a specific-clinical, clinical and partial-early response to treatment. Adverse effects (AEs) reported included; insomnia (34.2%) and headache (30.9%) among others. There were numerous significant associations between genotypes of HTR1A-RS6295 and AE of SSRI, However, on assessing the percentage of inflation of odds ratio, only the association between dizziness and CG genotype had an acceptable level of confounding (≤10%).


There were numerous association findings for AE treatment outcomes with genotypes of HTR1A-RS6295 in the current study. However, only the association of the CG genotype with dizziness was not marred by any confounding effect and thus was an accurate representation of true association. Therefore, this genotype holds a great potential for clinical utilisation in the near future for predicting dizziness.

Keywords: pharmacogenetic, SSRI (selective serotonergic reuptake inhibitors), adverse effect, efficacy, HTR1A

Oral 9.2

Acute Stress Induces Voluntary Alcohol Intake in Mice Through
Anxiety Mitigated By Toll-Like Receptor 4 Antagonist

Huei G. Chuang1, Sangu Muthuraju1*, Nur Naznee H. Abd Aziz1, Mustapha Muzaimi1, Jafri M. Abdullah1, 2 and Zamzuri Idris1, 2

1Department of Neurosciences, University of Science, Malaysia, Malaysia
2Center for Neuroscience Services and Research, University of Science, Malaysia, Malaysia

Corresponding author:Dr. Sangu Muthuraju, muthuraju67@gmail.com


Evidences previously supporting the functional involvement of toll-like receptor 4 (TLR4) in the mediation of neuroimmune system, further promoting the emergence of alcohol drinking behaviour following stress exposure. Thus, this study focused to investigate the effect of TLR4 antagonist Lipopolysaccharide-Rhodobacter Sphaeroides(LPS-RS) on the stress-induced voluntary alcohol drinking behaviour, neuronal component, and genes expression associating with stress and addiction.


This study involved the exposure of restraint and social isolation stress using Swiss Albino mice. Two-bottle choice ethanol exposure method was used in the evaluation of voluntary ethanol drinking behaviour. Several behavioural assessments including elevated plus-maze, light-dark box exploration, open field maze, beam walking test, and wire hanging test were carried out to assess the fear and anxiety-like behaviour, locomotion, motor coordination, and neuromuscular ability. Morphological and immunoreactivity analysis and genes expression analysis were done after the completion of behavioural assessments.


TLR4 antagonist LPS-RS treated stressed-mice showed a significant decrease in the ethanol intake compared to stressed mice. Behaviourally, acute stress did not cause any significant deficits on the motor coordination, neuromuscular ability, locomotion, exploratory behaviour and risk-assessment behaviour. Behavioural results proved that acute stress exposure causing the emergence of fear and anxiety-like behaviour in the stressed mice. Morphological analysis showed no significant changes in prefrontal cortex and hippocampus among all groups, while in immunoreactivity analysis, stressed-mice showed a significant increase immunoreactivity of c-FOS in both prefrontal cortex and hippocampus, significant increase immunoreactivity of TLR4 in prefrontal cortex and GFAP in hippocampus. Stressed-mice too showed significant increase in the TLR4, NF-Kappa, iNOS, DRD2, CREB-1, and OPRM-1 genes expression compared to control and LPS-RS treated mice.


TLR4 suppression using antagonist LPS-RS could be effective in reducing the ethanol intake among stress-exposed mice suggested that TLR4 suppression might provide a therapeutic value in the treatment of stress-induced alcohol addiction.

Keywords: Toll-like recepter 4 (TLR4), acute stress, Addiction, Alcohol drinking behavior, Lipopolysaccharide-Rhodobacter Sphaeroides(LPS-RS)

Oral 9.3

The effect of Som Jawa (Talinum triangulare) on BALB/c mice swimming time

Hardian Hardian1*, Yosef Purwoko1, Ainun R. Gumay1, Muflihatul Muniroh1, Darmawati A. Indraswari1 and Armita A. Apsari1

1Diponegoro University, Indonesia

Corresponding author:Dr. Hardian Hardian, dokterhardian@gmail.com


Som Jawa (Talinum triangulare) is a plant commonly found in Central Java that has been believed has potency as Korean Ginseng. The aim of the study is to investigate the effect of Som Jawa on mice swimming time as a parameter of physical endurance.


Study design was a pre-post test parallel groups design. Samples were male, 3 months old BALB/c mice (n=27). Mice were randomly allocated into 3 groups: Group I was given 18.2 mg of Som Jawa root extract in 0.5 cc aquadest, group II was given 0.5 cc supplement drink and Group III was given 0.5 cc aquadest. All treatments were given through gastric instillation once a day. Measured parameter is the length of swimming time. Swimming time were collected at day 0 (pre) and day 15 (post). Delta swimming time was calculated by substracting post – pre swimming time. The difference of swimming time of treatment group was analyzed using-Kruskall-Wallis and Mann-Whitney test.


Delta swimming time in Group I was 41.9±35.36 second, group II was 27.1±39.17 second and group III was 1.3±5.00 second. Group I was not significantly higher than group II (p=0.4), group I was significantly higher than group III (p=0.003). The difference between group II and group III was not significant (p=0.2).


Som Jawa (Talinum triangulare) administration increased swimming time of the mice.

Keywords: Javanese ginseng, Swimming time, ginseng, Mice, Endurance

Oral 9.6

Association of Sulfur Exposure to Attention Deficit Among Potato Farmers in Volcanic Area Dieng, Central Java, Indonesia

Saekhol Bakri1*, ainun r. gumay1, erni erni1, muflihatul muniroh1 and Hardian Hardian1

1Diponegoro University, Indonesia

Corresponding author: MD. Saekhol Bakri, saekhol1985@gmail.com


Volcanoes and their eruptions can result in many health impacts, which is an unconscious danger for community living nearby the area. Chronic exposure of sulfur in volcanic area may cause many health problem especially in nervous system and respiratory diseases. The aim of this study is to investigate the association of sulfur exposure to attention deficit among potato farmers in volcanic area Dieng, Indonesia.


A cross-sectional study was conducted. Participants were selected by purposive sampling method. Hair samples (about 200 mgr, around 1 cm from scalp) were collected from 24 participants. Sulfur concentrations were analyzed using SEM EDX method. Attention examination was measured by attention network test (ANT). Data were analyzed using Spearman correlation test.


Among 25 participants we found that mean of sulfur level was 10.867 ± 3.041. Higher sulfur were significantly correlated with poorer performance in total attention score (r = -0.447 ; p : 0.028), especially alerting (r= -0.416 ; p : 0.043) and executive function (r = -0.431 ; p< 0.035), but there were no corelation with orienting function.


Sulfur may affect on attention level especially in alerting and executive function.

Keywords: Volcanic area, Sulfur, Attention, Indonesia, Dieng

Oral 9.7

Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: Behavioural and ultra-structural approaches

Musa S. Chiroma1, 2, Mohamad A. Mohd Moklas2*, Mohamad T. Hidayat Baharuldin2, Che Norma M. Taib2, Zulkhairi Amom3 and Saravanan Jagadeesan4

1University of Maiduguri, Nigeria
2Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia
3Universiti Teknologi MARA Puncak Alam, Malaysia
4Universiti Tunku Abdul Rahman, Malaysia

Corresponding author: Dr. Mohamad A. Mohd Moklas, aris@upm.edu.my


Alzheimer’s disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent while aluminium is a known neurotoxin which is linked to pathogenesis of AD. The combined treatments of rats with D-gal and aluminium chloride (AlCl3) is considered as an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explores the protective effect of CA on cognition and brain ultra-structure in D-gal and AlCl3 induced rats.


Rats were exposed to D-gal 60mg/kg/bw/day + AlCl3 200mg/kg/bw/day and Centella asiatica (200, 400 and 800mg/kg/bw/day) or with donepezil (approved AD drug) 1mg/kg/bw/day for 70 days. Different cognitive paradigms; T maze spontaneous alternation, modified elevated plus maze, and novel object recognition task were used to evaluate full lesion of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl’s staining was used to determine the survival of hippocampus CA1 pyramidal cells while transmission electron microscopy was used to check the ultra-structural changes.


Our results showed that D-gal and AlCl3 could significantly impair behaviour and cognitive functions and cause damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultra-structural morphological alterations in the rat’s hippocampus. Conversely, co-administration with CA irrespective of dosage used alleviates the cognitive impairments and the pathological changes in the rats which is comparable to donepezil.


Taken together, these results suggest that CA could protect against cognitive impairments and morphological alterations caused by D-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA.

Keywords: Centella asiatica, cognitive impaiment, Hippocampus, Alheimer’s disease, Morphological alteration

Oral 9.8

Preliminary Studies of the Prevalence and Possible Clinical Consequences of Potential Simple and Multifactorial Drug and Gene Interactions of Anti-depressants in Older Australians

Mohitosh Biswas1*, Thilani H Dias2, Elizabeth Holliday2, Stephen Hancock2, John Attia2, Rodney J. Scott2, David Newby2, Karen P Kerr2 and Liz Milward2

1University of Rajshahi, Bangladesh
2University of Newcastle, Australia

Corresponding author:Dr. Mohitosh Biswas, biswas_07pharm@ru.ac.bd


Antidepressant drugs are often prescribed to treat psychiatric disorders in cancer patients. The safety or efficacy of these drugs may be affected by clinically significant drug-drug interactions (DDIs), drug gene interactions (DGIs) or combinations of these (multifactorial DGIs). The present study aimed to determine the prevalence of potential simple or multifactorial DGIs of participants taking antidepressant drugs of interest (TCAs or SSRIs) in older Australians where polypharmacy is common.


Co-prescribed interacting medications were identified from self-reported medication data of 2,642 participants aged over 55 in the Australian Hunter community study. Predicted drug and gene interactions were identified from genotyping data using Affymetrix Kaiser Axiom arrays and imputed data from the 1000 Genomes and HapMap Phase II European reference panels.Clinically significant pharmacogenotypes were identified from Clinical Pharmacogenetics Implementation Consortium (CPIC) pharmacogenomics based dosing guidelines.


Of the 270 participants on antidepressant drugs of interest (TCAs or SSRIs), 174 (64.4%; 95% CI 59%-70%) were co-prescribed at least one potential clinically significant interacting drug, with a mean of 1.6±0.8 possible interactions per participant. Genotype data were available for 128 of the 270 participants taking antidepressant drugs, with 15 participants (11.7%; 95% CI 6%-17%) identified as being at risk of clinically significant simple DGIs and 20 participants (15.6%; 95% CI 9%-22%) at risk of clinically significant multifactorial DGIs. These findings suggest a considerable proportion of participants using TCAs or SSRIs are at risk of drug and gene interactions affecting the safety or efficacy of these drugs.


Over 1/4 participants on antidepressants may be at increased risk of adverse reactions involving drug-gene interactions that may justify dose adjustment. This emphasizes the potential value of considering the pharmacogenomics of antidepressants in conjunction with drug interaction analyses.This should be taken into consideration when applying precision medicine approaches to improve outcomes in cancer patients.

Keywords: psychiatric disorders, Antidepressants, DDI, pharmacogenomics, precision medicine


Oral 10.1

Discovery of Novel Biocatalysts for Green Chemistry Reactions of Steroid

Sharifah N. Wan Yusop1, 2*, Sadia Sultan1, 2*, Syed A. Ali Shah1, 2 and Mohd I. Adenan3

1Faculty of Pharmacy, University Technology Mara, Malaysia
2Atta-ur-Rahman Institute for Natural Product Discovey, Universiti Teknologi MARA, Malaysia
3Faculty of Applied Sciences, Universiti Teknologi Mara, Malaysia

Corresponding author: Miss. Sharifah N. Wan Yusop, harifahnurfazilah@hotmail.com and Dr. Sadia Sultan, drsadia@salam.uitm.edu.my


There has been an upsurge of interest in biocatalysis especially in the field of synthetic biology for medicinal chemistry. Microbial-catalysed reactions have great potential as they speed up the drug discovery process and also promote sustainable practices for the generation of a diversified organic molecules notably natural products with complex structures like steroids. Steroid-based drugs is the highest marketed category of pharmaceuticals after antibiotics. This is due to steroid-based drugs having a wide range of therapeutic applications, such as anti-inflammatory, anti-tumour to neuroactive steroids, anti-allergy agents, and contraceptive agents. In the present work, biotransformation of medroxyprogesterone by a series of fungi from different biotopes has been investigated. The effect of the substrate modification in the biotransformed derivatives on the anti-proliferative activity was also examined.


Screening experiments were performed in 100 ml conical flasks containing 40 ml media and were autoclaved at 121°C for 15 minutes. Sterile culture media were inoculated with fungi. After 3-5 days of inoculation, substrates were introduced aseptically into fermented liquid media (0.5 mg/40 ml media) and further fermentations were allowed for 4-12 days. Preparative scale started upon detection of biotransformed products (BTPs). Anti-proliferative study of biotransformed products is based on the reduction of MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide).


Metabolic changes were observed by comparing the High Performance Liquid Chromatography (HPLC) chromatograms of starting compounds, control cultures and fermented extracts. Recent studies indicate incubation of medroxyprogesterone with fungi from different biotopes resulted BTPs. After separation and purification of the mixtures, complete spectrometric analysis were performed to verify the structures of transformed products. Selected BTPs along with the substrate were subjected to anti-proliferative assay.


Medroxyprogesterone is successfully transformed by fungi from different biotopes and selected BTPs have an anti-proliferative activity to some extent.

Keywords: Microbial transformation, Fungi, Medroxyprogesterone, Steroids, Sustainable Chemistry

Oral 10.2

Synthesis and Nitric Oxide Inhibitory Activities of New Xanthone Derivatives

Zi Han Loh1, Siau Hui Mah1*, Soek Sin Teh2 and Gwendoline Cheng Lian Ee3

1School of Biosciences, Taylor’s University, Malaysia
2Engineering and Processing Division, Malaysian Palm Oil Board, Malaysia
3Department of Chemistry, Putra Malaysia University, Malaysia

Corresponding author: Dr. Siau Hui Mah, siauhui.mah@taylors.edu.my


Xanthones attract great interest from researchers due to their broad pharmacological activities including anti-inflammation depending on the type of substituents and their relative position attached on the xanthone analogue. Increasing demands for effective anti-inflammatory drugs and limitation in obtaining xanthones from natural sources have led to us to synthesize a series of new xanthone derivatives with O-alkylation of 3-hydroxyxanthone to search for possible lead compounds in the treatment of anti-inflammatory diseases.


Alkylation was performed where 3-hydroxyxanthone and respective alkyl bromide were reacted with potassium carbonate in acetone with constant stirring under reflux for hours to synthesize xanthone derivatives. These xanthones were characterized by mass spectrometry (MS), nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) for structural elucidation. Xanthone derivatives were evaluated for their anti-inflammatory properties by measuring the inhibition effect of nitric oxide (NO) produced by LPS-induced RAW 264.7 cells.


A series of eleven alkyl substituted xanthone derivatives have been synthesized successfully. All the xanthone derivatives exhibited NO inhibition effects with the IC50 values in the range of 2.82 ± 0.20 to 24.27 ± 1.65 µg/mL, which are lower than the standard drug, diclofenac sodium with an IC50 value of 59.49 ± 1.09 µg/mL. The results indicated that these compounds possessed significant NO inhibition activities. Structure-activity relationship (SAR) study revealed that the xanthones with branched alkyl substituents showed stronger activities than the linear alkyl substituted xanthones. Among the derivatives, 3-(cyclobutylmethoxy)-9H-xanthen-9-one is the most potent NO inhibitor with an IC50 value of 2.82 ± 0.20 µg/mL.A series of eleven alkyl substituted xanthone derivatives have been synthesized successfully. All the xanthone derivatives exhibited NO inhibition effects with the IC50 values in the range of 2.82 ± 0.20 to 24.27 ± 1.65 µg/mL, which are lower than the standard drug, diclofenac sodium with an IC50 value of 59.49 ± 1.09 µg/mL. The results indicated that these compounds possessed significant NO inhibition activities. Structure-activity relationship (SAR) study revealed that the xanthones with branched alkyl substituents showed stronger activities than the linear alkyl substituted xanthones. Among the derivatives, 3-(cyclobutylmethoxy)-9H-xanthen-9-one is the most potent NO inhibitor with an IC50 value of 2.82 ± 0.20 µg/mL.


Different alkylated substituted xanthone derivatives have been successfully synthesized and showed significant NO inhibitory activity. The result suggested that C3 substituted cyclobutylmethoxy xanthone is a promising NO inhibitor. Thus, further studies on the molecular mechanism of this xanthone is proposed in due course.

Keywords: 3-hydroxyxanthone, Structure activity relationship (SAR), Alkyl substituents, anti-inflammation, Alkylation3-hydroxyxanthone, Structure activity relationship (SAR), Alkyl substituents, anti-inflammation, Alkylation

Oral 10.3

Dual compound loaded chitosan nanoparticles: synthesis and optimization

Nurhanisah Othman1, Mas Jaffri Masarudin2, 3, Cha Yee Kuen2, 3, Nurul Azira Dasuan1, Luqman Chuah Abdullah4 and Siti Nurul Ain Md Jamil1*

1Department of Chemistry, Faculty of Science, Putra Malaysia University, Malaysia
2Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Putra Malaysia University, Malaysia
3MAKNA Cancer Research, Institute of Bioscience, University Putra Malaysia, Malaysia
4Department of Chemical and Environmental Engineering, Faculty of Engineering, Universiti Putra Malaysia, Malaysia

Corresponding author: Dr. Siti Nurul Ain Md Jamil, ctnurulain@upm.edu.my 


Chitosan nanoparticles (CNP) have been tremendously studied for its excellent property as drug carrier. However, its hydrophilicity makes it more selective to certain pharmaceutical products. Encapsulation of both hydrophilic l-ascorbic acid (LAA) and hydrophobic thymoquinone (TQ) in CNP were investigated to augment its potential in delivering compounds.


CNP loaded with antioxidant LAA and TQ were synthesized via harmless ionic gelation routes. They were then characterized by using Fourier-Transform Infrared Spectroscopy (FTIR), nanosizer, UV-vis spectrophotometer and Field Emission Scanning Electron Microscope (FESEM).


The optimum CNP-LAA-TQ size produced was 141.5 ± 7.8 nm. The encapsulation efficiency of CNP-LAA-TQ was 22.8 ± 3.2 % for LAA and 35.6 ± 3.6 % for TQ.


The incorporation of hydrophilic LAA and hydrophobic TQ in a single CNP organization contributes in the advancement of multidrug therapy, especially in treating tuberculosis and cancers. The emergence of this dual compound nanoparticles is hoped to solve the issue of multitudinous potent drugs with low systemic uptake.

Keywords: antioxidant, Chitosan, Hydrophobic-hydrophilic, Ionic gelation, Nanoparticles

Oral 10.4

Synthesis of Dihydrobenzimidazoquinazoline Derivatives for Their Potential Biological Activities

Emilia Abdulmalek1, 2*, Mohd Basyaruddin Abdul Rahman1, 3, Khozirah Shaari1, 4, Hiba A. Hasan5 and Kim W. Chan6

1Department of Chemistry, Faculty of Science, Putra Malaysia University, Malaysia
2Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia,, Maldives
3Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia, Malaysia
4Laboratory of Natural Product, Institute of Bioscience, University Putra Malaysia, Malaysia
5College of Pharmacy, Al-Mustansiriya University, Iraq
6Laboratory of Molecular Biomedicine, Institute of Bioscience, University Putra Malaysia, Malaysia

Corresponding author: Dr. Emilia Abdulmalek, emilia@upm.edu.my


Heterocyclic compounds, whether natural or synthetic, are known for their vast biological activities and therapeutic potentials. Quinazoline and benzimidazoles derivatives have exhibited anti-tumour, anti-microbial, anti-viral, anti-tuberculosis and anti-inflammatory activities in separate occasion. Herein the synthesis of a series of dihydrobenzimidazoquinazoline derivatives was carried out as it was postulated that combination of these two heterocyclic moieties would exhibit excellent biological activities. Antioxidant activities of the compounds were screened as a low cost, predictive tool for their actual biological activities such as anticancer activity. The antibacterial and antifungal activities of the compounds were also evaluated.


Using microwave and conventional heating method, a series of dihydrobenzimidazoquinazoline derivatives (compound 1-7) was produced via condensation of 2-(2-aminophenyl)-1H-benzimidazole with a series of aliphatic aldehydes [propanal (1), butanal (2), isobutyraldehyde (3), hexanal (4), octanal (5), hydrocinnamaldehyde (6) and cinnamaldehyde (7)]. The anti-oxidant activities of the compounds were screened using two different methods: DPPH and ABTS scavenging activities. The antimicrobial activities of the compounds against four pathogenic bacteria (Staphyloccus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella choleraesuis) and one fungus (Aspergillus brasilliensis) were determined. Tetracycline (antibacterial) and nystatin (antifungal) were used as the positive control.


Seven (5 new) dihydrobenzimidazoquinazoline compounds were successfully synthesized and characterized. Both methods, microwave and conventional heating produced the compounds in excellent yield but the microwave method was far superior in term of the time needed to complete the reaction, only 5 mins compared to conventional heating (35 – 80 mins). All compounds showed moderate DPPH scavenging activities (13.95 – 24.54 mg/TE.g-1). Interestingly, the compounds exhibited excellent and better ABTS scavenging activities (382.70 – 774.2 mg/TE.g-1) and compound 1 with the smallest alkyl side chain (ethyl group) showed the best activities in both antioxidant tests. Compounds 1, 2 and 4 showed moderate activity against the Gram positive Staphyloccus aureus but only poor activity against Bacillus subtilis. All compounds showed no activity against the Gram negative bacteria (Pseudomonas aeruginosa, Salmonella choleraesuis) and the fungus (Aspergillus brasilliensis). Compounds bearing straight alkyl side chain showed better antibacterial activity than compounds having branch or aromatic side chain.


Synthesis of dihydrobenzimidazoquinazoline compounds was successful using both microwave and conventional heating. All compounds exhibited good antioxidant activity. Some compounds showed selective activity against Gram positive bacteria.

Keywords: dihydrobenzimidazoquinazoline, antioxidant, antimicrobial, Heterocyclic, Microwave

Oral 10.5

Biological Evaluation of Nano-colloidal Carrier Loaded with Cyclosporine, Potentially for Topical Treatment of Psoriasis

Norazlinaliza Salim1*, Siti Hajar Musa1 and Norashikin Shamsudin2

1Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia, Malaysia
2Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia

Corresponding author: Dr. Norazlinaliza Salim, azlinalizas@upm.edu.my


Psoriasis is known as a type of skin disease which easily spotted as dry skin with red and thick patches over the body. This has become a major problem for the patients as this skin type give uncomfortable feeling and a very itchy skin condition. This skin problem is a lifetime disease with no infinite cure due to the ineffectiveness of the drug release. In this study, the newly nanoemulsions formulation containing cyclosporine (an antipsoriatic drug) could be potential for psoriasis patients.


Cyclosporine-loaded nanoemulsion has been developed by a combination of low and high energy emulsification techniques. The formulation was then further evaluated on toxicity, colony counting, transepidermal water loss (TEWL), skin moisturizing effect and irritancy test.


From the results obtained, when cyclosporine was incorporated with the nanoemulsion carrier, its toxicity has been reduced. Their toxicity was recorded to be above the IC50 limit. In colony count analysis, results showed that after the spreading of nanoemulsion on the nutrient agar plate, it was found to have none of colony growth after 16-18 h of analysis. In TEWL and level of water content analysis showed that all volunteers gave significant positive results (P<0.05) with the reduction of TEWL as well as in skin’s water storage by all 15 volunteers. The highest increment of water uptake was 68.87 %. In irritancy analysis, the HIE score did not showed any irritant possibility towards the protein reagent. In addition, survey has also been carried out towards all volunteers on the effect of after 3 h application. None of them have reported to experience any skin irritancy, skin burning, skin inflammation or skin scaling.


Cyclosporine-loaded nanoemulsions have a good potential to be used for topical treatment of Psoriasis with good water storage for all volunteers’ skin with no record of irritancy side effect.

Keywords: Psoriasis, Cyclosporine, topical treatment, Colloidal carrier, Nanoemulsion

Oral 10.6

Establishing pre-clinical pharmacokinetic parameters for drug candidate using targeted mass spectrometry

Norazwana Samat1*, Wai Mun Kong2, Noreena Nordin2, Atiqah Tahziz2, Zamri Chik2and Pei Jean Tan1

1Cancer Research Malaysia, Malaysia
2Faculty of medicine, University of Malaya, Malaysia

Corresponding author:Mrs. Norazwana Samat, norazwana.samat@cancerresearch.my


Preclinical evaluation of drug candidate is important in the overall drug discovery process, mainly to address not only safety and efficacy but also the pharmacokinetics of a drug candidate. Pharmacokinetics studies the time course of drug absorption, distribution, metabolism and excretion. Liquid chromatography coupled with tandem quadrupole mass spectrometry (LC-TQMS) has been widely used as a tool to study pharmacokinetics, offering sensitive detection on wide dynamic range and selectivity on target molecules by multiple-reaction monitoring, which is critical for targeted quantification of candidate drugs in vivo.


To accurately quantify plasma level of our drug candidate, we adopted LC-TQMS as our tool. We first introduced our anti-cancer drug hit, ADF into LC-TQMS for optimal detection. Next, the optimized method was validated according to the ‘Bio-analytical method validation – Guidance for Industry’ from US-FDA, on the aspect of selectivity, accuracy, precision, recovery and stability of ADF. Following, calibration curves were generated and rat blood samples were collected at specific time points after intraperitoneal administration. Concentration of ADF in rat was quantified based on calibration curve. Pharmacokinetic parameters such as half-life, clearance and area under curve were determined using non-compartmental analysis.


From our analysis, ADF was detected optimally in negative ionization mode at transition of m/z 491.1 -> 217.2 and using Luna HILIC 3 µm particle size, 150 x 2.0 mm column for analytical separation. Calibration curve was generated over concentration range of 20 to 250 ng/mL with r2 = 0.99. Intra- and inter-day precision and accuracy was achieved as per guideline with <15% coefficient of variation. The overall pharmacokinetics properties of ADF is currently under investigation.


The state of the art for accurate quantification of drug candidates for the determination of pharmacokinetic properties has been established. Findings from this study have provided necessary guidance for lead optimization in the drug development process.

Keywords: pharmacokinetic, pre-clinical, Mass spectometry, Drug Discovery, Drug candidate

Oral 10.7

Association of Hair Total Mercury with Serum Ferritin Level Among Indonesian Pregnant Woman: A preliminary Study

Muflihatul Muniroh1*, Saekhol Bakri2, Ainun R. Gumay1, Julian Dewantiningrum3, Mulyono Mulyono3 and Hardian Hardian1

1Department of Physiology, Faculty of Medicine Diponegoro University, Indonesia
2Departement of Public Health, Faculty of Medicine Diponegoro University, Indonesia
3Department of Pediatrics, Faculty of Medicine Diponegoro University, Indonesia

Corresponding author: Dr. Muflihatul Muniroh, muflihatul.muniroh@fk.undip.ac.id


The exposure of Hg in pregnant women is an important issue since it can pass the placental blood barrier and affect to fetus. This study’s aim is to investigate the correlation between hair total mercury level with serum ferritin concentration in pregnancy mother to know whether Hg exposure may affect iron deficiency that have harmful effect in pregnancy. 


This is quantitative study with cross-sectional method design. Samples were 26 (from total 201 sample) pregnant mothers from 11 community health centers in Semarang, Central Java, Indonesia. Hg level from about 0.5mg of scalp hair was measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) method. Ferritin level was determined from serum blood using quantitively spectrophotometry.


As a preliminary result, total mercury (T-Hg) was determined from 26 hair sample of pregnant women, with mean level was 0.5810.288 (min-max: 0.009-1.204) mg/L. Serum ferritin mean level was 19.42611.301ng/mL (min-max: 2.54-52.51). Then ferritin was categorized as low level group <12ng/mL (n=5), normal >12ng/mL (n=21), and tested using Mann-Whitney U test. The result showed significant different between hair T-Hg level and serum ferritin (p=0.01) among pregnant women. Using correlation Spearman test, we found moderate correlation between increased hair T-Hg level and lower serum ferritrin (p=0.07, with r= -0.514). Subjects with T-Hg >0.7075mg/L had risk to have lower serum ferritin 8.0 x (95%CI=1.6-40.2).


The increased hair total mercury level is correlated with lower serum ferritin, indicating that mercury may affect an iron deficiency status in pregnant women.

Keywords: Hair total mercury, Serum ferritin, Iron deficiency, Pregnant women, Indonesia.

Oral 10.8

In vivo topical delivery of ethosomal formulation composed of Orthosiphon stamineus extract complexed with sophorolipid against melanoma

Mansoureh Nazari Vishkaei1, Mohamed Khadeer Ahamed Basheer2 and Amin Malik Shah Abdul Majid3*

1School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia
2Emanbiodiscoveries.sdn.bhd., Malaysia
3University of Science, Malaysia, Malaysia

Corresponding author: Prof. Amin Malik Shah Abdul Majid, aminmalikshah@gmail.com


Melanoma is one of the most aggressive types of skin cancers. Anti-angiogenic compounds can suppress melanoma cells. Orthosiphon stamineus (O.S) is a well-known herb with anticancer and anti-angiogenic effects. The health benefits of O.S extract is mainly due to its high antioxidant activity that can be attributed to rosmarinic acid (RA). However, RA has a limited ability to penetrate through the skin because of its hydrophilicity via topical application. The aim of this study is therefore to improve the penetrability of O.S extract through skin by sophorolipid (SL) nanovesicles, namely ethosome in mice.


Ethosome was made using thin film hydration method with sophorolipid as the surfactant. The ethosomal formulation of O.S (O.S-SL) was prepared at different concentrations and were physico-chemically characterized. Anti-angiogenic studies were then conducted. Anti-melanoma study was performed in albino mice using melanoma cell line (B16F10).


The optimized vesicle was 387nm in size with -35.6mV potential and exhibited 10 times better permeation ability when compared to the hydroethanolic solution of O.S extract. O.S-SL revealed 100% anti-angiogenic effect ex vivo and 95.8% anti-melanoma effect in vivo.


The results of this study demonstrated that O.S-SL can be absorbed efficiently via topical application to the deeper layers of the skin. The formulation has shown promising anti-angiogenic and anti-melanoma effects after topical applications.

Keywords: Orthosiphon stamineus, Ethosome, Sophorolipid, Melanoma, Topical


Speed Oral 11.1

Uncovering the Landscape of Somatic Mutations in Malaysian Colorectal Cancer Patients via Whole Genome Sequencing

Ryia Illani Mohd Yunos1, Nurul-Syakima Ab Mutalib1, Jia-Shiun Khoo2, Sazuita Saidin1, Muhiddin Ishak1, Nadiah Abu1, Najwa F. Mohd Yusof1, Norshahidah Mahamad Nazir1, Isa M. Rose3, Ismail Sagap4, Luqman Mazlan4 and Rahman Jamal1*

1UKM Medical Molecular Biology Institute (UMBI), Malaysia
2Codon Genomics, Malaysia
3Department of Pathology, Faculty of Medicine, National University of Malaysia, Malaysia
4Department of Surgery, Faculty of medicine, University of Malaya, Malaysia

Corresponding author: Prof. Rahman Jamal, rahmanj@ppukm.ukm.edu.my


Over the past few years, colorectal cancer (CRC) remains as the third most common cancer worldwide and the incidence are increasing continuously in some area of the world, including Malaysia. The expected rise of CRC burden in Malaysia underlines the importance of pushing ahead the pursuit of understanding this cancer by genetically profilling the genome of local CRC patients. In this study, we aimed to characterise the landscape of somatic mutations using whole genome sequencing approach, and to provide a better insight of the key molecular networks involved in Malaysian CRC patients.


Whole genome sequencing, with at least 30X coverage was performed on genomic DNA obtained from 28 CRC tissues. Identified variants were validated using Sanger sequencing. Expression of RNF43 gene in CRC tissues and cell lines was determined using qPCR.


All types of somatic mutations were detected and they included single nucleotide variants (SNVs), insertions and deletion in both coding as well as in non-coding region of the genome. With the mutation rate that ranged between 1 to 26 per 106, an average of 29, 318 SNVs in tumour samples were obtained. It was found that TP53 (10/13), APC (9/13) and KRAS (5/13) remained as the most commonly mutated genes in patients. Wnt signalling pathway was identified as the major affected pathway. At least one actionable somatic alteration was identified in all our patients. RNF43 mutation was likely to co-exist with BRAF V600E mutation in patient with MLH1 deficiency. RNF43 expression was upregulated in both CRC cell lines and tumour tissues; it was, however, downregulated in CRC tissue with RNF43 mutations (p.G156Afs and p.P192Gfs) when compared to the wild type.


This mutational signature analysis had illustrated the genomic landscape of CRC. Alternative treatment targeting Wnt signalling pathway could be beneficial to CRC patients carrying RNF43 mutations.

Keywords: colorectal cancer, whole genome sequencing, Molecular landscape, precision medicine, Wnt Signaling Pathway

Speed Oral 11.2

Efficacy of inhibition of BAD Ser99 phosphorylation by a novel small molecule in cisplatin resistant ovarian cancer

Yanxin Wang1*

1National University of Singapore, Singapore

Corresponding author:Ms. Yanxin Wang, wangyanxin98@gmail.com


Human BAD is a pro-apoptotic Bcl-2 family member, whose apoptotic functions can be inactivated through phosphorylation of specific residues including Ser99. Clinically, BAD phosphorylation has been reported to indicate poor survival and cisplatin resistance in ovarian cancer patients.


NPB, a novel small molecule which specifically inhibits BAD Ser99 phosphorylation, has been developed in our laboratory. Cell function assays performed include Alamar Blue cell viability assay, caspase3/7 assay, PI-Annexin V apoptosis assay, and 3D growth in Matrigel. The CI values are calculated using Chou-Talalay method. The cancer stem cell-like cell population was examined by ALDEFLOUR and sphere formation assays.


The level of BAD Ser99 phosphorylation is negatively correlated with cisplatin sensitivity in a panel of ovarian cancer cell lines and it is increased upon acute cisplatin treatment in ovarian cancer cells. The inhibition of BAD Ser99 phosphorylation by NPB alone increased apoptosis, decreased anchorage-independent growth of both parental and cisplatin resistant ovarian cancer cells, with the combination of NPB and cisplatin showing a synergistic effect. An upstream BAD kinase, AKT has also been reported to mediate cisplatin resistance. Correspondingly, the combination of NPB and AKT inhibitor AZD5363 exhibited strong synergistic effects in both parental and cisplatin resistant cell lines. Both the phosphorylation of BAD and its upstream kinase AKT was increased in this CSC-like population. NPB treatment alone was observed to decrease the CSC-like population, while the combination of AZD5363 and NPB produced a synergistic decrease in the CSC-like population.


NPB, as a novel inhibitor of BAD Ser99 phosphorylation, can potentially be used in combination with cisplatin as a therapy for naïve ovarian cancer patients to increase cisplatin sensitivity. Furthermore, the combination of NPB and AKT inhibitor AZD5363 is a potential therapeutic approach in the treatment of cisplatin resistant ovarian cancer.

Keywords: Bad phosphorylation, cisplatin resistance, ovarian cancer, NPB, Akt inhibitor

Speed Oral 11.4

Profiling of Exosomal Circular RNA in Folfox-Resistant Colon Cancer Cells

Kha Wai Hon1, Nadiah Abu1*, Nurul-Syakima Ab Mutalib1 and Rahman Jamal1

1UKM Medical Molecular Biology Institute (UMBI), Malaysia

Corresponding author: Dr. Nadiah Abu, nadiah.abu@ppukm.ukm.edu.my


Exosomes are extracellular nanovesicles released by almost all living cells including colorectal cancer cells (CRC) into biological fluids. Exosomes are natural carriers of proteins and nucleic acids that reflects parent cells. Exosomes have been investigated extensively as potential biomarkers and therapeutic targets for various diseases. However, the potential of exosomes as biomarkers to detect Folfox-resistant CRC has not been fully explored and validated. This research aimed to characterise exosomes derived from Folfox-resistant HCT116 CRC cell line as potential targets for further development of biomarkers among CRC patients with chemo-resistance.


Normal CRC cell line HCT116 (HCT116-C) was induced with 5 cycles of drug treatment to develop corresponding Folfox-resistant derivative clones (HCT116-R). HCT116-C and HCT116-R cell lines were compared for cell viability in 5-FU and oxaliplatin, wound healing assay, migration and invasion. Exosomes derived from both cell lines were characterised by transmission electron microscopy, particle size measurement, zeta potential analysis and Western Blot. Total RNA isolated from the exosomes of each cell line was subjected for circular RNA microarray. Selected circular RNAs were validated in clinical samples via RT-PCR.


As compared to normal HCT116-C cell line, HCT116-R cell line had higher IC50 values with 2.5 to 6-fold change. Migration rate of HCT116-R cell line was 19 percent higher than HCT116-C cell line in wound healing assay. Exosomes from both cell lines were morphologically cup-shaped nanovesicles that range from 60 to 370nm in size with zeta potential between -29.1mV and -16.3mV. 105 circular RNAs were upregulated and 34 circular RNAs were downregulated in exosomes derived from HCT116-R against HCT116-C cells.


We developed a stable HCT116-Folfox resistant CRC cells, and the characteristics of exosomes derived from parental and resistant cell lines is in concordance with the literature. We have identified several circular RNAs in exosomes as potential biomarkers to predict Folfox-responsiveness.

Keywords: colorectal cancer, molecular target, FOLFOX, biomarker, Exosomes