Publications by authors named "Hasni Arsad"

17 Publications

  • Page 1 of 1

Dichloromethane fraction of Moringa oleifera leaf methanolic extract selectively inhibits breast cancer cells (MCF7) by induction of apoptosis via upregulation of Bax, p53 and caspase 8 expressions.

Mol Biol Rep 2021 May 4;48(5):4465-4475. Epub 2021 Jun 4.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Kepala Batas, Penang, Malaysia.

Moringa oleifera is a well-known medicinal plant which has anti-cancer and other biological activities. This research aims to determine the cytotoxic and apoptotic effect of M. oleifera leave extract on the breast cancer (MCF7) cells. The extracts were prepared using hexane, dichloromethane, chloroform and n-butanol by fractionating the crude 80% methanol extract of the plant leaves. The cytotoxic effect of the extracts on MCF7 cells were determined using CellTiter 96® AQueous One Solution Cell Proliferation (MTS) assay. The apoptosis study was conducted using Annexin V-FITC analysis and confirmed by Western blotting using selected proteins, which are p53, Bax, cytochrome c and caspase 8. Our results showed that the dichloromethane (DF-CME-MOL) extract was selectively cytotoxic to MCF7 cells (5 μg/mL) without significantly inhibiting the non-cancerous breast (MCF 10A) cells. It had the highest selectivity index (SI) value of 9.5 among the tested extracts. It also induced early apoptosis and increased the expressions of pro-apoptotic proteins Bax, caspase 8 and p53 in MCF7 cells. Gas chromatography-mass spectrometry analysis (GC-MS) analysis showed that the major compounds found in DF-CME-MOL were benzeneacetonitrile, 4-hydroxy- and benzeneacetic acid, 4-hydroxy-, methyl ester among others that were detected. Thus, DF-CME-MOL extract was found to inhibit the proliferation of MCF7 cells by apoptosis induction, which is likely due to the activities of the detected phytochemical compounds of the extract.
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http://dx.doi.org/10.1007/s11033-021-06466-yDOI Listing
May 2021

Molecular docking of compounds from extract detected by GC-MS analysis with the SARS-CoV-2 main protease and ACE2 protein.

Nat Prod Res 2021 May 5:1-5. Epub 2021 May 5.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Penang, Malaysia.

has been reported to have many medicinal properties and it is traditionally used in treating viral lesions. This study aims to determine the molecular docking of compounds detected by Gas Chromatography-Mass Spectrometry (GC-MS) with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 main protease) protein and its host receptor angiotensin-converting enzyme 2 (ACE2) protein using the AutoDock 4.2 tool. The drug-likeness and molecular docking analyses showed that fourteen compounds of satisfied the Lipinski's rule of five and they exhibited good inhibitory effects against the SARS-Cov-2 main protease and ACE2 proteins. In addition, the glyceryl 2-linolenate compound was found to have the most potent binding affinities with both proteins. The results provide useful insights into the molecular inhibitory interactions of compounds detected by GC-MS analysis with the targeted SARS-CoV-2 main protease and ACE2 protein.
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http://dx.doi.org/10.1080/14786419.2021.1919104DOI Listing
May 2021

Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants.

Plants (Basel) 2020 Oct 12;9(10). Epub 2020 Oct 12.

Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Kepala Batas, Penang, Malaysia.

The zebrafish () is used as an embryonic and larval model to perform in vitro experiments and developmental toxicity studies. Zebrafish may be used to determine the toxicity of samples in early screening assays, often in a high-throughput manner. The zebrafish embryotoxicity model is at the leading edge of toxicology research due to the short time required for analyses, transparency of embryos, short life cycle, high fertility, and genetic data similarity. Zebrafish toxicity studies range from assessing the toxicity of bioactive compounds or crude extracts from plants to determining the optimal process. Most of the studied extracts were polar, such as ethanol, methanol, and aqueous solutions, which were used to detect the toxicity and bioactivity. This review examines the latest research using zebrafish as a study model and highlights its power as a tool for detecting toxicity of medicinal plants and its effectiveness at enhancing the understanding of new drug generation. The goal of this review was to develop a link to ethnopharmacological zebrafish studies that can be used by other researchers to conduct future research.
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http://dx.doi.org/10.3390/plants9101345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601530PMC
October 2020

-Mediated Silver Nanoparticles Inhibited Acute Myeloid Leukemia (AML) Kasumi-1 Cells by Inducing Cell Cycle Arrest.

Bioinorg Chem Appl 2020 22;2020:8898360. Epub 2020 Sep 22.

School of Biological Sciences, Universiti Sains Malaysia, 11800 George Town, Penang, Malaysia.

Background: Acute myeloid leukemia (AML) persists to be a major health problem especially among children as effective chemotherapy to combat the disease is yet to be available. is a well-known herb that is traditionally used for treatment and management of many diseases including degenerative diseases. In this study, silver nanoparticles were synthesized from the phytochemicals of stem bark aqueous extract. The silver nanoparticles were characterized by carrying out Fourier Transform Infrared (FTIR) spectroscopy, Energy Filtered Scanning Electron Microscopy (FESEM), X-ray diffraction, and Dynamic Light Scattering (DLS) analyses. Antioxidant capacity of the nanoparticles was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the antiproliferative effect of the nanoparticles on Kasumi-1 leukemia cells was investigated using PrestoBlue assay. Flow cytometry analysis was performed to observe the effect of the nanoparticles on the leukemia cell cycle progression.

Results: Our findings revealed that the synthesized silver nanoparticles were formed from electrons of the plant phytochemicals which include aromatic compounds, ethers, and alkynes. FESEM analysis revealed that the sizes of the nanoparticles range from 12 nm to 101 nm; however, DLS analysis estimated a larger average size of the nanoparticles (108.3 nm) because it measured the hydrodynamic radii of the nanoparticles. The zeta potential of the nanoparticles was -16 nm, and the XRD pattern of the nanoparticles has distinct peaks at 38.02°, 42.94°, 64.45°, 77.20°, and 81.47°, which is typical of face-centered cubic (fcc) structure of silver. The Trolox Equivalence Antioxidant Capacity (TEAC) of the nanoparticles was estimated to be 300.91 M Trolox/mg silver nanoparticles. The nanoparticles inhibited Kasumi-1 cell proliferation. The half minimal inhibitory concentrations (IC50s) that inhibited Kasumi-1 cell proliferation are 49.5 g/ml and 13.25 g/ml at 48 and 72 hours, respectively. The nanoparticles induced cell cycle arrest in the Kasumi-1 cells at S (5% increase) and G2/M (3% increase) phases.

Conclusion: The nanoparticles synthesized from the stem bark extract of inhibit the growth of Kasumi-1 leukemia cells by activating cell cycle arrest; thus, they are potential antileukemic agents.
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http://dx.doi.org/10.1155/2020/8898360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528135PMC
September 2020

Inhibitory Effect of Eco-Friendly Naturally Synthesized Silver Nanoparticles from the Leaf Extract of Medicinal Detarium microcarpum Plant on Pancreatic and Cervical Cancer Cells.

Asian Pac J Cancer Prev 2020 May 1;21(5):1247-1252. Epub 2020 May 1.

School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Pulau Pinang, Malaysia.

Background: Recently, nanoparticle synthesis by eco-friendly methods has received tremendous attention due to the method advantages and also because of the application of the nanoparticles in cancer research. Therefore, in this study, we synthesized silver nanoparticles from Detarium microcarpum leaf phytochemicals and evaluated its inhibitory effect on pancreatic and cervical cancer cells.

Materials And Methods: Silver nanoparticles (dAgNps) were synthesized by reacting phytochemicals of D. microcarpum leaves with silver nitrate for 12 hours. Cell viability assay was carried out to investigate the cytotoxic effect of dAgNps on HeLa and PANC-1 cells.

Results: Scanning electron microscopy (SEM) and transmission electron microscopy(TEM) results revealed the average sizes of dAgNps are 81 nm and 84 nm respectively. The x-ray diffraction (XRD) pattern of dAgNps was similar to that of face centered cubic(fcc) structure of silver as reported by joint committee on powder diffraction standards (JCPDS) and fourier-transform infrared spectroscopy (FTIR) analysis showed that some phytochemicals of D. microcarpum such as polyphenols and flavonoids were likely involved in the reduction of Ag+ to form nanoparticles. Finally, cell viability assay revealed dAgNps inhibited PANC-1 and HeLa cell proliferations with IC50 values of 84 and 31.5 µg/ml respectively.

Conclusion: In conclusion, the synthesized nanoparticles from D. microcarpum leaves (dAgNps) have inhibitory effect on pancreatic and cervical cancer cells.
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http://dx.doi.org/10.31557/APJCP.2020.21.5.1247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541888PMC
May 2020

Antioxidant Effects, Antiproliferative Effects, and Molecular Docking of Leaf Extracts.

Molecules 2020 Apr 29;25(9). Epub 2020 Apr 29.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas 13200, Penang, Malaysia.

is a well-known herb that has been used as an alternative and therapeutic medicine, however more selective extracts are needed. In this study, leaves were extracted with 80% methanol and further fractionated with -hexane, dichloromethane, chloroform, n-butanol, and aqueous residue. Subsequently, the total phenolic content (TPC), total flavonoid content (TFC), antioxidant scavenging activity, and antiproliferative effects on breast cancer (Michigan Cancer Foundation-7 [MCF7]) and normal breast (Michigan Cancer Foundation-10A [MCF 10A]) cells of the extracts were measured. Additionally, molecular docking simulation of the major compounds from extracts was conducted. The aqueous residue had the highest TPC and TFC, whereas the crude extract had the highest scavenging activity. Among the extracts, dichloromethane extract (CN-Dcm) was selected as it had the highest selectivity index (SI) (1.48). Then, the chosen extract (CN-Dcm) was proceed for further analysis. The compounds from CN-Dcm were identified using gas chromatography-mass spectrometry (GC-MS). The major compounds from CN-Dcm were further investigated through molecular docking studies. Palmitic acid and linolenyl alcohol were the compounds found in the CN-Dcm extract that exhibited the highest binding affinities with p53-binding protein Mdm-2. These results highlight the potential of as a source of anticancer activities.
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http://dx.doi.org/10.3390/molecules25092067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249086PMC
April 2020

Corrigendum to ", , and Induce Apoptosis and Cell Cycle Arrest and Inhibit Metastasis on MCF7 Breast Cancer Cells".

Evid Based Complement Alternat Med 2019;2019:1529570. Epub 2019 Sep 8.

Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Pulau Pinang, Malaysia.

[This corrects the article DOI: 10.1155/2019/6104574.].
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http://dx.doi.org/10.1155/2019/1529570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754871PMC
September 2019

Induce Apoptosis and Cell Cycle Arrest and Inhibit Metastasis on MCF7 Breast Cancer Cells.

Evid Based Complement Alternat Med 2019 23;2019:6104574. Epub 2019 May 23.

Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Pulau Pinang, Malaysia.

Despite the availability of anticancer drugs, breast cancer remains the most death-causing tumor-related disease in women. Hence, there is a need for discovery and development of efficient alternative drugs, and sources such as plants need to be explored. In this study, antioxidant capacities and inhibitory effects against MCF7 cells of the extracts of stem bark of three Nigerian medicinal plants (, and ) were investigated. The extracts had the highest antioxidant and antiproliferative effects, followed by that of , and the extracts had minimal effects. The IC values of the methanol and aqueous extracts from the three plants that inhibited the proliferation of MCF7 cells ranged from 78-> 500 g/ml. Moreover, all the plant extracts but the aqueous extract of exhibited antimetastatic action and induced apoptosis and cell cycle arrest in MCF7 cells. Liquid chromatography/time-of-flight/mass spectrometry profiling revealed that the five potent extracts contain many phenols and omega-6 fatty acids, and some of the identified compounds (isorhamnetin, eupatorin, alpinumisoflavone, procyanidin B3, syringin, and gallic acid) have been reported to have antiproliferative effects on cancer cells. Hence, the stem bark of these plants could be potential sources of antibreast cancer agents.
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http://dx.doi.org/10.1155/2019/6104574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556270PMC
May 2019

In Vitro Cytotoxic Activity of Clinacanthus nutans Leaf Extracts Against HeLa Cells

Asian Pac J Cancer Prev 2019 Feb 26;20(2):601-609. Epub 2019 Feb 26.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia. Email:

Objective: This study was conducted to investigate the antiproliferative activity of extracts of Clinacanthus nutans leaves against human cervical cancer (HeLa) cells. Methods: C. nutans leaves were subjected to extraction using 80% methanol or water. The methanol extract was further extracted to obtain hexane, dichloromethane (DCM), and aqueous fractions. The antiproliferative activity of the extracts against HeLa cells was determined. The most cytotoxic extract was furthered analyzed by apoptosis and cell cycle assays, and the phytochemical constituents were screened by gas chromatography-mass spectrometry (GC-MS). Results: All of the extracts were antiproliferative against HeLa cells, and the DCM fraction had the lowest IC50 value of 70 μg/mL at 48 h. Microscopic studies showed that HeLa cells exposed to the DCM fraction exhibited marked morphological features of apoptosis. The flow cytometry study also confirmed that the DCM fraction induced apoptosis in HeLa cells, with cell cycle arrest at the S phase. GC-MS analysis revealed the presence of at least 28 compounds in the DCM fraction, most of which were fatty acids. Conclusion: The DCM fraction obtained using the extraction method described herein had a lower IC50 value than those reported in previous studies that characterized the anticancer activity of C. nutans against HeLa cells.
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http://dx.doi.org/10.31557/APJCP.2019.20.2.601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897000PMC
February 2019

Total Phenolics, Total Flavonoids, Antioxidant Capacities, and Volatile Compounds Gas Chromatography-Mass Spectrometry Profiling of Ripe Seed Polar Fractions.

Pharmacogn Mag 2018 Apr-Jun;14(54):191-194. Epub 2018 Apr 10.

Bitechnology Unit, School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Pulau Pinang, Malaysia.

Background: Academic reports have confirmed leaves to possess significant antioxidant capacities; however, such studies are unavailable for its ripe seeds even though they are more desirous for consumption due to their sweet taste.

Objective: In this study, we investigated antioxidant capacities of four polar extracts (crude water, ethanol, butanol, and aqueous residue) from the plant's ripe seeds.

Materials And Methods: Phytochemicals were extracted from the ripe seeds of using ethanol and water solvents at initial stage. Butanol and aqueous residue were then subsequently fractioned out from the ethanol extract. Phenolic and flavonoid contents of the polar extracts were determined. Then, their antioxidant capacities were quantified by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Finally, gas chromatography-mass spectrometry (GC-MS) analyses of the extracts were performed.

Results: DPPH and ABTS tests showed that the polar extracts possess significant antioxidant capacities that ranged from 29 to 35.408 μM Trolox equivalence antioxidant capacity (TEAC)/mg sample and 7 to 29 μM TEAC/mg sample, respectively. The antioxidant capacities of the extracts corresponded to their phenolic and flavonoid contents that varied from 13.61 to 20.42 mg gallic acid equivalence/g sample and 0.58 to 9.81 mg quercetin equivalence/g sample, respectively. Finally, GC-MS analyses revealed antimicrobial phenolic compounds, 4-hydroxybenzaldehyde in crude water extract and 4-hydroxybenzene acetonitrile in the ethanol and butanol extracts, and aqueous residue.

Conclusion: Our results established that ripe seeds have significant antioxidant activity which may be due to its phenolic and nonphenolic compounds content.

Summary: In this study, polar phytochemicals from ripe seeds of were extracted by water and ethanol solvents, and butanol extract and aqueous residue were subsequently fractioned out of the ethanol extract. The four polar extracts were shown to have significant antioxidant capacities which correspond to their phenolic contents. Further, antimicrobial compounds 4-hydroxybenzaldehyde and 4-hydroxybenzene acetonitrile were identified in the extracts by gas chromatography-mass spectrometry analyses. ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); DPPH: 2,2-diphenyl-1-picrylhydrazyl; TEAC: Trolox equivalence antioxidant capacity; QE: Quercetin equivalence; GAE: Gallic acid equivalence; GC-MS: Gas chromatography-mass spectrometry.
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http://dx.doi.org/10.4103/pm.pm_212_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909314PMC
April 2018

Assessment of three plastid DNA barcode markers for identification of (Acanthaceae).

3 Biotech 2018 Jan 11;8(1):62. Epub 2018 Jan 11.

2School of Biological Sciences, Universiti Sains Malaysia, 11800 Gelugor, Penang Malaysia.

This study was conducted to determine the feasibility of using three plastid DNA regions (, -, and ) as DNA barcodes to identify the medicinal plant . In this study, was collected at several different locations. Total genomic DNA was extracted, amplified by polymerase chain reaction (PCR), and sequenced using , -, and , primers. DNA sequences generated from PCR were submitted to the National Center for Biotechnology Information's (NCBI) GenBank. Identification of was carried out using NCBI's Basic Local Alignment Search Tool (BLAST). The and - regions successfully identified with sequencing rates of 100% through BLAST identification. Molecular Evolutionary Genetics Analysis (MEGA) 6.0 was used to analyze interspecific and intraspecific divergence of plastid DNA sequences. and exhibited the lowest average interspecific distance (0.0487 and 0.0963, respectively), whereas - exhibited the highest average interspecific distance (0.2029). The R package Spider revealed that - correctly identified Barcode of Life Data System (BOLD) 96%, best close match 79%, and near neighbor 100% of the species, compared to (BOLD 72%; best close match 64%; near neighbor 78%) and (BOLD 77%; best close match 62%; near neighbor 88%). These results indicate that - is very effective at identifying , as it performed well in discriminating species in Acanthaceae.
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http://dx.doi.org/10.1007/s13205-018-1092-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762596PMC
January 2018

Structure of polyhydroxyalkanoate (PHA) synthase PhaC from Chromobacterium sp. USM2, producing biodegradable plastics.

Sci Rep 2017 07 13;7(1):5312. Epub 2017 Jul 13.

Structural Biology Laboratory, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.

Polyhydroxyalkanoate (PHA) is a promising candidate for use as an alternative bioplastic to replace petroleum-based plastics. Our understanding of PHA synthase PhaC is poor due to the paucity of available three-dimensional structural information. Here we present a high-resolution crystal structure of the catalytic domain of PhaC from Chromobacterium sp. USM2, PhaC -CAT. The structure shows that PhaC -CAT forms an α/β hydrolase fold comprising α/β core and CAP subdomains. The active site containing Cys291, Asp447 and His477 is located at the bottom of the cavity, which is filled with water molecules and is covered by the partly disordered CAP subdomain. We designated our structure as the closed form, which is distinct from the recently reported catalytic domain from Cupriavidus necator (PhaC -CAT). Structural comparison showed PhaC -CAT adopting a partially open form maintaining a narrow substrate access channel to the active site, but no product egress. PhaC -CAT forms a face-to-face dimer mediated by the CAP subdomains. This arrangement of the dimer is also distinct from that of the PhaC -CAT dimer. These findings suggest that the CAP subdomain should undergo a conformational change during catalytic activity that involves rearrangement of the dimer to facilitate substrate entry and product formation and egress from the active site.
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http://dx.doi.org/10.1038/s41598-017-05509-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509742PMC
July 2017

ANTIPROLIFERATIVE EFFECT ON BREAST CANCER (MCF7) OF SEED EXTRACTS.

Afr J Tradit Complement Altern Med 2017 13;14(2):282-287. Epub 2017 Jan 13.

School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Pulau Pinang, Malaysia.

Background: belongs to plant family, Moringaceae and popularly called "wonderful tree", for it is used traditionally to cure many diseases including cancer in Africa and Asia, however, there is limited knowledge on cytotoxic activity of seeds on MCF7 breast cancer cell. The present study evaluated antiproliferative effect on MCF7 of the seed.

Materials And Methods: Seeds of were grinded to powder and its phytochemicals were extracted using water and 80% ethanol solvents, part of the ethanolic extract were sequentially partitioned to fractions with four solvents (hexane, dichloromethane, chloroform, and n-butanol). Antiproliferative effects on MCF7 of the samples were determined. Finally, potent samples that significantly inhibited MCF7 growth were tested on MCF 10A.

Results: Crude water extract, hexane and dichloromethane fractions of the seeds inhibited the proliferation of MCF7 with the following IC values 280 μg/ml, 130 μg/ml and 26 μg/ml respectively, however, of the 3 samples, only hexane fraction had minimal cytotoxic effect on MCF 10A (IC > 400μg/ml).

Conclusion: seed has antiproliferative effect on MCF7.
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http://dx.doi.org/10.21010/ajtcam.v14i2.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446454PMC
August 2017

Evaluation of genetic diversity of (Acanthaceaea) using RAPD, ISSR and RAMP markers.

Physiol Mol Biol Plants 2016 Oct 31;22(4):523-534. Epub 2016 Oct 31.

Central Drug Research Institute, Universiti Sains Malaysia, 11800 Gelugor, Penang Malaysia.

Three polymerase chain reaction (PCR) techniques were compared to analyse the genetic diversity of eight populations in the northern region of Peninsular Malaysia. The PCR techniques were random amplified polymorphic deoxyribonucleic acids (RAPD), inter-simple sequence repeats (ISSR) and random amplified microsatellite polymorphisms (RAMP). Leaf genomic DNA was PCR amplified using 17 RAPD, 8 ISSR and 136 RAMP primers . However, only 10 RAPD primers, 5 ISSR primers and 37 RAMP primers produced reproducible bands. The results were evaluated for polymorphic information content (PIC), marker index (MI) and resolving power (RP). The RAMP marker was the most useful marker compared to RAPD and ISSR markers because it showed the highest average value of PIC (0.25), MI (11.36) and RP (2.86). The genetic diversity showed a high percentage of polymorphism at the species level compared to the population level. Furthermore, analysis of molecular variance revealed that the genetic diversity was higher within populations, as compared to among populations of . From the results, the RAMP technique was recommended for the analysis of genetic diversity of
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http://dx.doi.org/10.1007/s12298-016-0391-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120048PMC
October 2016

Biophysical changes of ATP binding pocket may explain loss of kinase activity in mutant DAPK3 in cancer: A molecular dynamic simulation analysis.

Gene 2016 Apr 31;580(1):17-25. Epub 2015 Dec 31.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200 Bertam, Pulau Pinang, Malaysia. Electronic address:

DAPK3 belongs to family of DAPK (death-associated protein kinases) and is involved in the regulation of progression of the cell cycle, cell proliferation, apoptosis and autophagy. It is considered as a tumor suppressor kinase, suggesting the loss of its function in case of certain specific mutations. The T112M, D161N and P216S mutations in DAPK3 have been observed in cancer patients. These DAPK3 mutants have been associated with very low kinase activity, which results in the cellular progression towards cancer. However, a clear understanding of the structural and biophysical variations that occur in DAPK3 with these mutations, resulting in the decreased kinase activity has yet not been deciphered. We performed a molecular dynamic simulation study to investigate such structural variations. Our results revealed that mutations caused a significant structural variation in DAPK3, majorly concentrated in the flexible loops that form part of the ATP binding pocket. Interestingly, D161N and P216S mutations collapsed the ATP binding pocket through flexible loops invasion, hindering ATP binding which resulted in very low kinase activity. On the contrary, T112M mutant DAPK3 reduces ATP binding potential through outward distortion of flexible loops. In addition, the mutant lacked characteristic features of the active protein kinase including proper interaction between HR/FD and DFG motifs, well structured hydrophobic spine and Lys42-Glu64 salt bridge interaction. These observations could possibly explain the underlying mechanism associated with the loss of kinase activity with T112M, D161N and P216S mutation in DAPK3.
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http://dx.doi.org/10.1016/j.gene.2015.12.066DOI Listing
April 2016

Molecular docking and dynamic simulation evaluation of Rohinitib - Cantharidin based novel HSF1 inhibitors for cancer therapy.

J Mol Graph Model 2015 Sep 22;61:141-9. Epub 2015 Jul 22.

Advanced Centre for Bioengineering and Bioinformatics (ACBB), Integral Research Centre (IRC), Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh 226026, India. Electronic address:

Recent developments in the target based cancer therapies have identified HSF1 as a novel non oncogenic drug target. The present study delineates the design and molecular docking evaluation of Rohinitib (RHT) - Cantharidin (CLA) based novel HSF1 inhibitors for target-based cancer therapy. Here, we exploited the pharmacophoric features of both the parent ligands for the design of novel hybrid HSF1 inhibitors. The RHT-CLA ligands were designed and characterized for ADME/Tox features, interaction with HSF1 DNA binding domain and their pharmacophoric features essential for interaction. From the results, amino acid residues Ala17, Phe61, His63, Asn65, Ser68, Arg71 and Gln72 were found crucial for HSF1 interaction with the Heat shock elements (HSE). The hybrid ligands had better affinity towards the HSF1 DNA binding domain, in comparison to RHT or CLA and interacted with most of the active site residues. Additionally, the HSF1-ligand complex had a reduced affinity towards HSE in comparison to native HSF1. Based on the results, ligand RC15 and RC17 were non carcinogenic, non mutagenic, completely biodegradable under aerobic conditions, had better affinity for HSF1 (1.132 and 1.129 folds increase respectively) and diminished the interaction of HSF1 with HSE (1.203 and 1.239 folds decrease respectively). The simulation analysis also suggested that the ligands formed a stable complex with HSF1, restraining the movement of active site residues. In conclusion, RHT-CLA hybrid ligands can be used as a potential inhibitor of HSF1 for non-oncogene target based cancer therapy.
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http://dx.doi.org/10.1016/j.jmgm.2015.07.003DOI Listing
September 2015

Cloning and Characterisation of (R)-3-hydroxyacyl-acyl Carrier Protein-coenzyme A Transferase Gene (phaG) from Pseudomonas sp. USM 4-55.

Trop Life Sci Res 2009 Dec;20(2):1-14

School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Pulau Pinang, Malaysia.

The (R)-3-hydroxyacyl-ACP-CoA transferase catalyses the conversion of (R)-3-hydroxyacyl-ACP to (R)-3-hydroxyacyl-CoA derivatives, which serves as the ultimate precursor for polyhydroxyalkanoate (PHA) polymerisation from unrelated substrates in pseudomonads. PhaG was found to be responsible for channelling precursors for polyhydroxyalkanoate (PHA) synthase from a de novo fatty acid biosynthesis pathway when cultured on carbohydrates, such as glucose or gluconate. The phaG gene was cloned from Pseudomonas sp. USM 4-55 using a homologous probe. The gene was located in a 3660 bp Sal I fragment (GenBank accession number EU305558). The open reading frame (ORF) was 885 bp long and encoded a 295 amino acid protein. The predicted molecular weight was 33251 Da, and it showed a 62% identity to the PhaG of Pseudomonas aeruginosa. The function of the cloned phaG of Pseudomonas sp. USM 4-55 was confirmed by complementation studies. Plasmid pBCS39, which harboured the 3660 bp Sal I fragment, was found to complement the PhaG-mutant heterologous host cell, Pseudomonas putida PhaGN-21. P. putida PhaGN-21, which harboured pBCS39, accumulated PHA that accounted for up to 18% of its cellular dry weight (CDW). P. putida PhaGN-21, which harboured the vector alone (PBBR1MCS-2), accumulated only 0.6% CDW of PHA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819057PMC
December 2009
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