Siaw Hwang - Academia.edu (original) (raw)

Papers by Siaw Hwang

Research paper thumbnail of Simple and Rapid Characterization of Sarawak Stingless Bee Honey Using Melissopalynological and Atr-Ftir Analysis

Research paper thumbnail of Optimal Aeration Management Strategy for A Small-Scale Food Waste Composting

Carbon Resources Conversion

Research paper thumbnail of In vitro Cytotoxic Activities, Molecular Docking and Density Functional Theory (DFT) Evaluation of Chalcone Derived Pyrazolines

Chemistry Africa, 2022

Chalcone natural products modified drugs are a significant tool for the pharmaceutical industry t... more Chalcone natural products modified drugs are a significant tool for the pharmaceutical industry to cure cancer. Numerous cytotoxic drugs have some drawbacks such as toxicity effect, high cost, less bioavailability, poor selectivity and drug resistance properties. The production of effective and high potent cytotoxic agents has become a challenge nowadays. For all compounds (1a–f), (2a–f) and (3a–f) in vitro cytotoxic activities were evaluated through MTS assay, where (3a) and (3e) exhibited potent activities against nasopharyngeal cell line HK-1 with IC50 7.7 mM and 7.3 mM, respectively, compared to cisplatin IC50 8.9 mM. The molecular docking interaction studies against 5IKR target protein and DFT evaluations via Gaussian 09 software exhibited the binding affinity – 10.4 kcal/mol and energy gap 4.46 eV respectively, supported the potential pyrazoline as anticancer drugs. This current study is a significant breakthrough in the drug design process that contributes to the development of new in vitro cytotoxic drugs with excellent properties.

Research paper thumbnail of Quantitative Proteomics Profiling of Silvestrol-treated Nasopharynx Cancer Cell Lines

Research paper thumbnail of pH‐Responsive Starch‐Citrate Nanoparticles for Controlled Release of Paracetamol

Starch - Stärke, 2019

Starch‐citrate samples with degrees of substitution (DS) ranging from 0.11 to 0.90 are synthesize... more Starch‐citrate samples with degrees of substitution (DS) ranging from 0.11 to 0.90 are synthesized by a green esterification reaction between citric acid and native sago starch (Metroxylon sagu) in an aqueous medium. Starch‐citrate nanoparticles with mean diameter of 105 nm are subsequently obtained by controlled precipitation through drop‐wise addition of dissolved starch‐citrate solution into excess absolute ethanol. These nanoparticles are observed to exhibit pH‐responsive release profiles within the physiological pH range of 1.2–8.6. The release profile of a model drug (paracetamol) is observed to obey the zero‐order kinetics, with the release mechanism based on the diffusion and swelling model. The cytotoxicity study in HaCaT cell lines (human skin cells) shows that starch‐citrate nanoparticles are non‐toxic and hence are suitable for biomedical applications as pH‐responsive drug carriers.

Research paper thumbnail of In vitro cytotoxicity evaluation of thiourea derivatives bearing Salix sp. constituent against HK-1 cell lines

Natural Product Research, 2018

In searching for drugs from natural product scaffolds has gained interest among researchers. In t... more In searching for drugs from natural product scaffolds has gained interest among researchers. In this study, a series of twelve halogenated thiourea (ATX 1-12) via chemical modification of aspirin (a natural product derivative) and evaluated for cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines, HK-1 via MTS-based colorimetric assay. The cytotoxicity studies demonstrated that halogens at meta position of ATX showed promising activity against HK-1 cells (IC 50 value 15 mM) in comparison to cisplatin, a positive cytotoxic drug (IC 50 value ¼8.9 ± 1.9 mM). ATX 11, bearing iodine at meta position, showed robust cytotoxicity against HK-1 cells with an IC 50 value of 4.7 ± 0.7 mM. Molecular docking interactions between ATX 11 and cyclooxygenase-2 demonstrated a robust binding affinity value of À8.1 kcal/mol as compared to aspirin's binding affinity value of À6.4 kcal/mol. The findings represent a promising lead molecule from natural product with excellent cytotoxic activity against NPC cell lines.

Research paper thumbnail of Gene isolation using degenerate primers targeting protein motif: A laboratory exercise

Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology, Jan 13, 2017

Structures and functions of protein motifs are widely included in many biology-based course sylla... more Structures and functions of protein motifs are widely included in many biology-based course syllabi. However, little emphasis is placed to link this knowledge to applications in biotechnology to enhance the learning experience. Here, the conserved motifs of nucleotide binding site-leucine rich repeats (NBS-LRR) proteins, successfully used for the isolation and characterization of many plant resistance gene analogues (RGAs), is featured in the development of a series of laboratory experiments using important molecular biology techniques. A set of previously isolated RGA sequences is used as the model for performing sequence alignment and visualising 3D protein structure using current bioinformatics programs (Clustal Omega and Argusdock software). A pair of established degenerate primer sequences is provided for the prediction of targeted amino acids sequences in the RGAs. Reverse transcription-polymerase chain reaction (RT-PCR) is used to amplify RGAs from total RNA samples extracted...

Research paper thumbnail of Effects of acute salt stress on modulation of gene expression in a Malaysian salt-tolerant indigenous rice variety, Bajong

Journal of Plant Research, 2017

samples were then compared, leading to the discovery of 4096 DEGs. Based on the functional annota... more samples were then compared, leading to the discovery of 4096 DEGs. Based on the functional annotation results obtained, the enrichment factor of each functional group in DEGs was calculated in relation to the total reads obtained. It was found that the group with the highest gene modulation was involved in the secondary metabolite biosynthesis of plants, with approximately 2.5% increase in relation to the total reads obtained. This suggests an extensive transcriptional reprogramming of the secondary metabolic pathways after stress induction, which could be directly responsible for the salt tolerance capability of Bajong. Keywords mRNA-seq • Wild rice variety • Antioxidant content • Salt stress • Plant phytochemicals Abbreviations COG Clusters of orthologous groups DEGs Differentially expressed genes DPPH Di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium GMO Genetically modified organism GO Gene ontology KEGG Kyoto encyclopedia of gene and genome LEA Late embryogenesis abundant ROS Reactive oxygen species RWC Relative water content SOS Salt overly sensitive TFC Total flavonoid content TPC Total phenolic content

Research paper thumbnail of Bioassay-Guided Fractionation of Wound Healing Active Compounds From <I>Piper nigrum</I> L. Berries Extract in Malaysia

UK Journal of Pharmaceutical Biosciences, 2018

The study aimed to further evaluate the wound healing property of P. nigrum L. using bioassay-gui... more The study aimed to further evaluate the wound healing property of P. nigrum L. using bioassay-guided fractionation method. The ethanolic extract of Piper nigrum L. was fractionated in two stages using column chromatography and preparative reversed phase C18 HPLC, respectively. Significant wound healing properties screened using the scratch wound assay was observed through the cell migration assay in fraction number three (PNE3) out of the 14 fractions, exhibiting 36.7% and 43.8% closure of wound gap within 20 hours at concentration of 0.3 and 1.0 µg/mL, respectively. Sub-fractions which were further fractionated from PNE3 showed comparatively reduced wound healing activity using the same bioassay. The sub-fractions were also compared to Piperine, a major component of P. nigrum L. and the results were comparable. This experimental study revealed that Piperine works together with other compounds in P. nigrum L. to improve wound healing as claimed by those home remedy.

Research paper thumbnail of Identification of Potential p38γ Inhibitors via In Silico Screening, In Vitro Bioassay and Molecular Dynamics Simulation Studies

International Journal of Molecular Sciences

Protein kinase p38γ is an attractive target against cancer because it plays a pivotal role in can... more Protein kinase p38γ is an attractive target against cancer because it plays a pivotal role in cancer cell proliferation by phosphorylating the retinoblastoma tumour suppressor protein. Therefore, inhibition of p38γ with active small molecules represents an attractive alternative for developing anti-cancer drugs. In this work, we present a rigorous and systematic virtual screening framework to identify potential p38γ inhibitors against cancer. We combined the use of machine learning-based quantitative structure activity relationship modelling with conventional computer-aided drug discovery techniques, namely molecular docking and ligand-based methods, to identify potential p38γ inhibitors. The hit compounds were filtered using negative design techniques and then assessed for their binding stability with p38γ through molecular dynamics simulations. To this end, we identified a promising compound that inhibits p38γ activity at nanomolar concentrations and hepatocellular carcinoma cell ...

Research paper thumbnail of Authentication of geographical growth origin of black pepper (piper nigrum l.) based on volatile organic compounds profile: A case study for Malaysia and India black peppers

2019 IEEE International Symposium on Olfaction and Electronic Nose (ISOEN)

Black pepper is one of the common spices used in foods as a favoring agent. Their utilization is ... more Black pepper is one of the common spices used in foods as a favoring agent. Their utilization is diversified into other applications such as pepper spray for defense, medicine for healthcare and pest control in the agriculture sector. In order to meet the industry demand, various countries with a suitable tropical climate have grown black pepper as one of their export commodities. Indirectly, reputation and quality of the black pepper are associated with the growth origin as the soil quality, handling processes, and growing environment will influence the final grade of the black pepper. Geographical origin has become one of the parameters in determining the price of the pepper. In view of this, there is a pressing demand to have a standard to identify the growth origin of black pepper to avoid counterfeit issues with the intention to scope for higher market price. This paper reports an attempt to determine the growth origin of black pepper (Piper nigrum L.) based on the volatile organic compounds (VOCs) profile recorded using high resolution gas chromatography mass spectrometry system. In this work, black peppers from two different countries of origin; namely from Malaysia and India were selected as a case study. A total of 252 of black pepper samples from these two origins were extracted for non-polar compounds using a standard method and the VOCs profiles were then subjected to Principal Component Analysis (PCA) and Fold Change Analysis. PCA cluster plots showed that Indian and Malaysian black pepper can be confidently discriminated by means of unique non-polar compounds present in the pepper samples.

Research paper thumbnail of In-silico discovery of inhibitors against human papillomavirus E1 protein

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Repurposing FDA-approved drugs as HIV-1 integrase inhibitors: an in silico investigation

Journal of Biomolecular Structure and Dynamics, 2022

The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million... more The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million lives to-date. One of the most efficacious treatments for naïve or pretreated HIV patients is the HIV integrase strand transfer inhibitors (INSTIs). However, given that HIV treatment is life-long, the emergence of HIV strains resistant to INSTIs is an imminent challenge. In this work, we showed two best regression QSAR models that were constructed using a boosted Random Forest algorithm (r2 = 0.998, q210CV = 0.721, q2external_test = 0.754) and a boosted K* algorithm (r2 = 0.987, q210CV = 0.721, q2external_test = 0.758) to predict the pIC50 values of INSTIs. Subsequently, the regression QSAR models were deployed against the Drugbank database for drug repositioning. The top-ranked compounds were further evaluated for their target engagement activity using molecular docking studies and accelerated Molecular Dynamics simulation. Lastly, their potential as INSTIs were also evaluated from our literature search. Our study offers the first example of a large-scale regression QSAR modelling effort for discovering highly active INSTIs to combat HIV infection.Communicated by Ramaswamy H. Sarma.

Research paper thumbnail of Regression QSAR Models for Predicting HIV-1 Integrase Inhibitors

The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million... more The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million lives to date. One of the most efficacious treatment for naïve or pre-treated HIV patients is with the HIV integrase strand transfer inhibitors (INSTIs). However, given that HIV treatment is lifelong, the emergence of HIV-1 strains resistant to INSTIs is an imminent challenge. In this work, we showed two best regression QSAR models that were constructed using a boosted Random Forest algorithm (r2 = 0.998, q210CV = 0.721, q2external_test = 0.754) and a boosted K* algorithm (r2 = 0.987, q210CV = 0.721, q2external_test = 0.758) to predict the pIC50 values of INSTIs. Subsequently, the regression QSAR models were deployed against the Drugbank database for drug repositioning. The top ranked compounds were further evaluated for their target engagement activity using molecular docking studies and their potential as INSTIs evaluated from our literature search. Our study offers the first example ...

Research paper thumbnail of Distribution of the CYP2C19*17 allele in multi-ethnic Malaysian patients with coronary artery disease planned for percutaneous coronary intervention

Research paper thumbnail of Multi-ethnic distribution of ABCB1 C3435T polymorphism and its association with ADP-induced platelet aggregation on patients receiving clopidogrel treatment

Research paper thumbnail of Evaluation of Deep Learning for Image-based Black Pepper Disease and Nutrient Deficiency Classification

2021 2nd International Conference on Artificial Intelligence and Data Sciences (AiDAS), 2021

Black pepper (Piper nigrum) diseases and nutrient deficiency can often be observed based on the s... more Black pepper (Piper nigrum) diseases and nutrient deficiency can often be observed based on the symptoms exerted on its leaves. This paper aimed to investigate the effectiveness of employing a deep learning approach to classify black pepper disease and nutrient deficiency based on leaf images. We constructed a customized convolutionary neural network to determine how its training parameters would affect the prediction performances. Another two deep learning neural networks VGG16 and Inception V3, are also employed for comparisons. We have sampled 947 images from farms in Sarawak consisted of 8 classes in total. Image augmentation is performed on the images to produce a total of 9532 images. The result shows that the customized CNN performed slightly better than the other two deep learning approaches at a 0.98 sensitivity rate. Furthermore, image augmentation contributed to improving prediction performance for all the deep learning models. This study has demonstrated that deep learning is a feasible approach for classifying black pepper diseases and nutrient deficiency based on leaf images.

Research paper thumbnail of Plant growth-promoting bacteria as potential bio-inoculants and biocontrol agents to promote black pepper plant cultivation

Microbiological Research, 2020

Plant growth-promoting bacteria as potential bio-inoculants and biocontrol agents to promote blac... more Plant growth-promoting bacteria as potential bio-inoculants and biocontrol agents to promote black pepper plant cultivation Ee Tiing Lau (Conceptualization)ce:contributor-roleResearch) (Methodology)ce:contributor-roleExperiments) (Formal analysis) (Data curation) (Investigation) (Visualization) (Writing-review and editing), Akio Tani (Validation) (Writing-review and editing), Choy Yuen Khew (Project administration) (Resources), Yee Qin Chua (Methodology)ce:contributor-roleExperiments) (Formal analysis) (Investigation), Siaw San Hwang (Supervision) (Validation) (Writing-review and editing)

Research paper thumbnail of Antioxidative attributes of rice bran extracts in ameliorative effects of atherosclerosis-associated risk factors

Heliyon, 2020

Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical e... more Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor-α (TNF-α), interleukin (IL)-α (IL-1α), IL-1β, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPSstimulated protein expressions of iNOS, TNF-α, IL-1α, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/β2-glycoprotein I (oxLDL/β2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr À/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-α, IL-1β) and hepatic (TNF-α, IL-1α, IL-1β) proinflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis.

Research paper thumbnail of Corrigendum to “Cytoprotective and Cytotoxic Effects of Rice Bran Extracts in Rat H9c2(2-1) Cardiomyocytes”

Oxidative Medicine and Cellular Longevity, 2018

Research paper thumbnail of Simple and Rapid Characterization of Sarawak Stingless Bee Honey Using Melissopalynological and Atr-Ftir Analysis

Research paper thumbnail of Optimal Aeration Management Strategy for A Small-Scale Food Waste Composting

Carbon Resources Conversion

Research paper thumbnail of In vitro Cytotoxic Activities, Molecular Docking and Density Functional Theory (DFT) Evaluation of Chalcone Derived Pyrazolines

Chemistry Africa, 2022

Chalcone natural products modified drugs are a significant tool for the pharmaceutical industry t... more Chalcone natural products modified drugs are a significant tool for the pharmaceutical industry to cure cancer. Numerous cytotoxic drugs have some drawbacks such as toxicity effect, high cost, less bioavailability, poor selectivity and drug resistance properties. The production of effective and high potent cytotoxic agents has become a challenge nowadays. For all compounds (1a–f), (2a–f) and (3a–f) in vitro cytotoxic activities were evaluated through MTS assay, where (3a) and (3e) exhibited potent activities against nasopharyngeal cell line HK-1 with IC50 7.7 mM and 7.3 mM, respectively, compared to cisplatin IC50 8.9 mM. The molecular docking interaction studies against 5IKR target protein and DFT evaluations via Gaussian 09 software exhibited the binding affinity – 10.4 kcal/mol and energy gap 4.46 eV respectively, supported the potential pyrazoline as anticancer drugs. This current study is a significant breakthrough in the drug design process that contributes to the development of new in vitro cytotoxic drugs with excellent properties.

Research paper thumbnail of Quantitative Proteomics Profiling of Silvestrol-treated Nasopharynx Cancer Cell Lines

Research paper thumbnail of pH‐Responsive Starch‐Citrate Nanoparticles for Controlled Release of Paracetamol

Starch - Stärke, 2019

Starch‐citrate samples with degrees of substitution (DS) ranging from 0.11 to 0.90 are synthesize... more Starch‐citrate samples with degrees of substitution (DS) ranging from 0.11 to 0.90 are synthesized by a green esterification reaction between citric acid and native sago starch (Metroxylon sagu) in an aqueous medium. Starch‐citrate nanoparticles with mean diameter of 105 nm are subsequently obtained by controlled precipitation through drop‐wise addition of dissolved starch‐citrate solution into excess absolute ethanol. These nanoparticles are observed to exhibit pH‐responsive release profiles within the physiological pH range of 1.2–8.6. The release profile of a model drug (paracetamol) is observed to obey the zero‐order kinetics, with the release mechanism based on the diffusion and swelling model. The cytotoxicity study in HaCaT cell lines (human skin cells) shows that starch‐citrate nanoparticles are non‐toxic and hence are suitable for biomedical applications as pH‐responsive drug carriers.

Research paper thumbnail of In vitro cytotoxicity evaluation of thiourea derivatives bearing Salix sp. constituent against HK-1 cell lines

Natural Product Research, 2018

In searching for drugs from natural product scaffolds has gained interest among researchers. In t... more In searching for drugs from natural product scaffolds has gained interest among researchers. In this study, a series of twelve halogenated thiourea (ATX 1-12) via chemical modification of aspirin (a natural product derivative) and evaluated for cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines, HK-1 via MTS-based colorimetric assay. The cytotoxicity studies demonstrated that halogens at meta position of ATX showed promising activity against HK-1 cells (IC 50 value 15 mM) in comparison to cisplatin, a positive cytotoxic drug (IC 50 value ¼8.9 ± 1.9 mM). ATX 11, bearing iodine at meta position, showed robust cytotoxicity against HK-1 cells with an IC 50 value of 4.7 ± 0.7 mM. Molecular docking interactions between ATX 11 and cyclooxygenase-2 demonstrated a robust binding affinity value of À8.1 kcal/mol as compared to aspirin's binding affinity value of À6.4 kcal/mol. The findings represent a promising lead molecule from natural product with excellent cytotoxic activity against NPC cell lines.

Research paper thumbnail of Gene isolation using degenerate primers targeting protein motif: A laboratory exercise

Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology, Jan 13, 2017

Structures and functions of protein motifs are widely included in many biology-based course sylla... more Structures and functions of protein motifs are widely included in many biology-based course syllabi. However, little emphasis is placed to link this knowledge to applications in biotechnology to enhance the learning experience. Here, the conserved motifs of nucleotide binding site-leucine rich repeats (NBS-LRR) proteins, successfully used for the isolation and characterization of many plant resistance gene analogues (RGAs), is featured in the development of a series of laboratory experiments using important molecular biology techniques. A set of previously isolated RGA sequences is used as the model for performing sequence alignment and visualising 3D protein structure using current bioinformatics programs (Clustal Omega and Argusdock software). A pair of established degenerate primer sequences is provided for the prediction of targeted amino acids sequences in the RGAs. Reverse transcription-polymerase chain reaction (RT-PCR) is used to amplify RGAs from total RNA samples extracted...

Research paper thumbnail of Effects of acute salt stress on modulation of gene expression in a Malaysian salt-tolerant indigenous rice variety, Bajong

Journal of Plant Research, 2017

samples were then compared, leading to the discovery of 4096 DEGs. Based on the functional annota... more samples were then compared, leading to the discovery of 4096 DEGs. Based on the functional annotation results obtained, the enrichment factor of each functional group in DEGs was calculated in relation to the total reads obtained. It was found that the group with the highest gene modulation was involved in the secondary metabolite biosynthesis of plants, with approximately 2.5% increase in relation to the total reads obtained. This suggests an extensive transcriptional reprogramming of the secondary metabolic pathways after stress induction, which could be directly responsible for the salt tolerance capability of Bajong. Keywords mRNA-seq • Wild rice variety • Antioxidant content • Salt stress • Plant phytochemicals Abbreviations COG Clusters of orthologous groups DEGs Differentially expressed genes DPPH Di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium GMO Genetically modified organism GO Gene ontology KEGG Kyoto encyclopedia of gene and genome LEA Late embryogenesis abundant ROS Reactive oxygen species RWC Relative water content SOS Salt overly sensitive TFC Total flavonoid content TPC Total phenolic content

Research paper thumbnail of Bioassay-Guided Fractionation of Wound Healing Active Compounds From <I>Piper nigrum</I> L. Berries Extract in Malaysia

UK Journal of Pharmaceutical Biosciences, 2018

The study aimed to further evaluate the wound healing property of P. nigrum L. using bioassay-gui... more The study aimed to further evaluate the wound healing property of P. nigrum L. using bioassay-guided fractionation method. The ethanolic extract of Piper nigrum L. was fractionated in two stages using column chromatography and preparative reversed phase C18 HPLC, respectively. Significant wound healing properties screened using the scratch wound assay was observed through the cell migration assay in fraction number three (PNE3) out of the 14 fractions, exhibiting 36.7% and 43.8% closure of wound gap within 20 hours at concentration of 0.3 and 1.0 µg/mL, respectively. Sub-fractions which were further fractionated from PNE3 showed comparatively reduced wound healing activity using the same bioassay. The sub-fractions were also compared to Piperine, a major component of P. nigrum L. and the results were comparable. This experimental study revealed that Piperine works together with other compounds in P. nigrum L. to improve wound healing as claimed by those home remedy.

Research paper thumbnail of Identification of Potential p38γ Inhibitors via In Silico Screening, In Vitro Bioassay and Molecular Dynamics Simulation Studies

International Journal of Molecular Sciences

Protein kinase p38γ is an attractive target against cancer because it plays a pivotal role in can... more Protein kinase p38γ is an attractive target against cancer because it plays a pivotal role in cancer cell proliferation by phosphorylating the retinoblastoma tumour suppressor protein. Therefore, inhibition of p38γ with active small molecules represents an attractive alternative for developing anti-cancer drugs. In this work, we present a rigorous and systematic virtual screening framework to identify potential p38γ inhibitors against cancer. We combined the use of machine learning-based quantitative structure activity relationship modelling with conventional computer-aided drug discovery techniques, namely molecular docking and ligand-based methods, to identify potential p38γ inhibitors. The hit compounds were filtered using negative design techniques and then assessed for their binding stability with p38γ through molecular dynamics simulations. To this end, we identified a promising compound that inhibits p38γ activity at nanomolar concentrations and hepatocellular carcinoma cell ...

Research paper thumbnail of Authentication of geographical growth origin of black pepper (piper nigrum l.) based on volatile organic compounds profile: A case study for Malaysia and India black peppers

2019 IEEE International Symposium on Olfaction and Electronic Nose (ISOEN)

Black pepper is one of the common spices used in foods as a favoring agent. Their utilization is ... more Black pepper is one of the common spices used in foods as a favoring agent. Their utilization is diversified into other applications such as pepper spray for defense, medicine for healthcare and pest control in the agriculture sector. In order to meet the industry demand, various countries with a suitable tropical climate have grown black pepper as one of their export commodities. Indirectly, reputation and quality of the black pepper are associated with the growth origin as the soil quality, handling processes, and growing environment will influence the final grade of the black pepper. Geographical origin has become one of the parameters in determining the price of the pepper. In view of this, there is a pressing demand to have a standard to identify the growth origin of black pepper to avoid counterfeit issues with the intention to scope for higher market price. This paper reports an attempt to determine the growth origin of black pepper (Piper nigrum L.) based on the volatile organic compounds (VOCs) profile recorded using high resolution gas chromatography mass spectrometry system. In this work, black peppers from two different countries of origin; namely from Malaysia and India were selected as a case study. A total of 252 of black pepper samples from these two origins were extracted for non-polar compounds using a standard method and the VOCs profiles were then subjected to Principal Component Analysis (PCA) and Fold Change Analysis. PCA cluster plots showed that Indian and Malaysian black pepper can be confidently discriminated by means of unique non-polar compounds present in the pepper samples.

Research paper thumbnail of In-silico discovery of inhibitors against human papillomavirus E1 protein

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Repurposing FDA-approved drugs as HIV-1 integrase inhibitors: an in silico investigation

Journal of Biomolecular Structure and Dynamics, 2022

The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million... more The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million lives to-date. One of the most efficacious treatments for naïve or pretreated HIV patients is the HIV integrase strand transfer inhibitors (INSTIs). However, given that HIV treatment is life-long, the emergence of HIV strains resistant to INSTIs is an imminent challenge. In this work, we showed two best regression QSAR models that were constructed using a boosted Random Forest algorithm (r2 = 0.998, q210CV = 0.721, q2external_test = 0.754) and a boosted K* algorithm (r2 = 0.987, q210CV = 0.721, q2external_test = 0.758) to predict the pIC50 values of INSTIs. Subsequently, the regression QSAR models were deployed against the Drugbank database for drug repositioning. The top-ranked compounds were further evaluated for their target engagement activity using molecular docking studies and accelerated Molecular Dynamics simulation. Lastly, their potential as INSTIs were also evaluated from our literature search. Our study offers the first example of a large-scale regression QSAR modelling effort for discovering highly active INSTIs to combat HIV infection.Communicated by Ramaswamy H. Sarma.

Research paper thumbnail of Regression QSAR Models for Predicting HIV-1 Integrase Inhibitors

The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million... more The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million lives to date. One of the most efficacious treatment for naïve or pre-treated HIV patients is with the HIV integrase strand transfer inhibitors (INSTIs). However, given that HIV treatment is lifelong, the emergence of HIV-1 strains resistant to INSTIs is an imminent challenge. In this work, we showed two best regression QSAR models that were constructed using a boosted Random Forest algorithm (r2 = 0.998, q210CV = 0.721, q2external_test = 0.754) and a boosted K* algorithm (r2 = 0.987, q210CV = 0.721, q2external_test = 0.758) to predict the pIC50 values of INSTIs. Subsequently, the regression QSAR models were deployed against the Drugbank database for drug repositioning. The top ranked compounds were further evaluated for their target engagement activity using molecular docking studies and their potential as INSTIs evaluated from our literature search. Our study offers the first example ...

Research paper thumbnail of Distribution of the CYP2C19*17 allele in multi-ethnic Malaysian patients with coronary artery disease planned for percutaneous coronary intervention

Research paper thumbnail of Multi-ethnic distribution of ABCB1 C3435T polymorphism and its association with ADP-induced platelet aggregation on patients receiving clopidogrel treatment

Research paper thumbnail of Evaluation of Deep Learning for Image-based Black Pepper Disease and Nutrient Deficiency Classification

2021 2nd International Conference on Artificial Intelligence and Data Sciences (AiDAS), 2021

Black pepper (Piper nigrum) diseases and nutrient deficiency can often be observed based on the s... more Black pepper (Piper nigrum) diseases and nutrient deficiency can often be observed based on the symptoms exerted on its leaves. This paper aimed to investigate the effectiveness of employing a deep learning approach to classify black pepper disease and nutrient deficiency based on leaf images. We constructed a customized convolutionary neural network to determine how its training parameters would affect the prediction performances. Another two deep learning neural networks VGG16 and Inception V3, are also employed for comparisons. We have sampled 947 images from farms in Sarawak consisted of 8 classes in total. Image augmentation is performed on the images to produce a total of 9532 images. The result shows that the customized CNN performed slightly better than the other two deep learning approaches at a 0.98 sensitivity rate. Furthermore, image augmentation contributed to improving prediction performance for all the deep learning models. This study has demonstrated that deep learning is a feasible approach for classifying black pepper diseases and nutrient deficiency based on leaf images.

Research paper thumbnail of Plant growth-promoting bacteria as potential bio-inoculants and biocontrol agents to promote black pepper plant cultivation

Microbiological Research, 2020

Plant growth-promoting bacteria as potential bio-inoculants and biocontrol agents to promote blac... more Plant growth-promoting bacteria as potential bio-inoculants and biocontrol agents to promote black pepper plant cultivation Ee Tiing Lau (Conceptualization)ce:contributor-roleResearch) (Methodology)ce:contributor-roleExperiments) (Formal analysis) (Data curation) (Investigation) (Visualization) (Writing-review and editing), Akio Tani (Validation) (Writing-review and editing), Choy Yuen Khew (Project administration) (Resources), Yee Qin Chua (Methodology)ce:contributor-roleExperiments) (Formal analysis) (Investigation), Siaw San Hwang (Supervision) (Validation) (Writing-review and editing)

Research paper thumbnail of Antioxidative attributes of rice bran extracts in ameliorative effects of atherosclerosis-associated risk factors

Heliyon, 2020

Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical e... more Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor-α (TNF-α), interleukin (IL)-α (IL-1α), IL-1β, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPSstimulated protein expressions of iNOS, TNF-α, IL-1α, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/β2-glycoprotein I (oxLDL/β2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr À/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-α, IL-1β) and hepatic (TNF-α, IL-1α, IL-1β) proinflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis.

Research paper thumbnail of Corrigendum to “Cytoprotective and Cytotoxic Effects of Rice Bran Extracts in Rat H9c2(2-1) Cardiomyocytes”

Oxidative Medicine and Cellular Longevity, 2018