Publications by authors named "Mohd Nizam Mordi"

17 Publications

  • Page 1 of 1

Comparative Toxicity Assessment of Kratom Decoction, Mitragynine and Speciociliatine Versus Morphine on Zebrafish () Embryos.

Front Pharmacol 2021 20;12:714918. Epub 2021 Aug 20.

Centre for Drug Research, Universiti Sains Malaysia, George Town, Malaysia.

Kratom ( Korth), a popular opioid-like plant holds its therapeutic potential in pain management and opioid dependence. However, there are growing concerns about the safety or potential toxicity risk of kratom after prolonged use. The study aimed to assess the possible toxic effects of kratom decoction and its major alkaloids, mitragynine, and speciociliatine in comparison to morphine in an embryonic zebrafish model. The zebrafish embryos were exposed to kratom decoction (1,000-62.5 μg/ml), mitragynine, speciociliatine, and morphine (100-3.125 μg/ml) for 96 h post-fertilization (hpf). The toxicity parameters, namely mortality, hatching rate, heart rate, and morphological malformations were examined at 24, 48, 72, and 96 hpf, respectively. Kratom decoction at a concentration range of ≥500 μg/ml caused 100% mortality of zebrafish embryos and decreased the hatching rate in a concentration-dependent manner. Meanwhile, mitragynine and speciociliatine exposure resulted in 100% mortality of zebrafish embryos at 100 μg/ml. Both alkaloids caused significant alterations in the morphological development of zebrafish embryos including hatching inhibition and spinal curvature (scoliosis) at the highest concentration. While exposure to morphine induced significant morphological malformations such as pericardial oedema, spinal curvature (lordosis), and yolk edema in zebrafish embryos. Our findings provide evidence for embryonic developmental toxicity of kratom decoction and its alkaloids both mitragynine and speciociliatine at the highest concentration, hence suggesting that kratom consumption may have potential teratogenicity risk during pregnancy and thereby warrants further investigations.
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http://dx.doi.org/10.3389/fphar.2021.714918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417521PMC
August 2021

Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside.

Infect Genet Evol 2021 09 28;93:104944. Epub 2021 May 28.

Centre for Drug Research, Universiti Sains Malaysia, USM, 11800 Pulau Pinang, Malaysia. Electronic address:

Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest. This review comprehensively highlights the common pathomechanisms and pharmacological targets of HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2, and potent therapeutic potentials from basic and clinical experimental investigations. The implicated targets for the prevention and treatment include the viral proteases (M, PL, 3CL), viral structural proteins (S- and N-proteins), non-structural proteins (nsp 3, 8, 10, 14, 16), accessory protein (ns12.9), viroporins (3a, E, 8a), enzymes (RdRp, TMPRSS2, ADP-ribosyltransferase, MTase, 2'-O-MTase, TATase, furin, cathepsin, deamidated human triosephosphate isomerase), kinases (MAPK, ERK, PI3K, mTOR, AKT, Abl2), interleukin-6 receptor (IL-6R) and the human host receptor, ACE2. Notably among the 109 overviewed inhibitors include quercetin, eriodictyol, baicalin, luteolin, melatonin, resveratrol and berberine from natural products, GC373, NP164 and HR2P-M2 from peptides, 5F9, m336 and MERS-GD27 from specific human antibodies, imatinib, remdesivir, ivermectin, chloroquine, hydroxychloroquine, nafamostat, interferon-β and HCQ from repurposing libraries, some iron chelators and traditional medicines. This review represents a model for further translational studies for effective anti-CoV therapeutic designs.
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http://dx.doi.org/10.1016/j.meegid.2021.104944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159710PMC
September 2021

Neuropharmacological potentials of β-carboline alkaloids for neuropsychiatric disorders.

Eur J Pharmacol 2021 Feb 25;893:173837. Epub 2020 Dec 25.

Centre for Drug Research, Universiti Sains Malaysia, USM, 11800, Pulau Pinang, Malaysia. Electronic address:

Neuropsychiatric disorders are diseases of the central nervous system (CNS) which are characterised by complex pathomechanisms that including homeostatic failure, malfunction, atrophy, pathology remodelling and reactivity anomaly of the neuronal system where treatment options remain challenging. β-Carboline (βC) alkaloids are scaffolds of structurally diverse tricyclic pyrido[3,4-b]indole alkaloid with vast occurrence in nature. Their unique structural features which favour interactions with enzymes and protein receptor targets account for their potent neuropharmacological properties. However, our current understanding of their biological mechanisms for these beneficial effects, especially for neuropsychiatric disorders is sparse. Therefore, we present a comprehensive review of the scientific progress in the last two decades on the prospective pharmacology and physiology of the βC alkaloids in the treatment of some neuropsychiatric conditions such as depression, anxiety, Alzheimer's disease, Parkinson's disease, brain tumour, essential tremor, epilepsy and seizure, licking behaviour, dystonia, agnosia, spasm, positive ingestive response as demonstrated in non-clinical models. The current evidence supports that βC alkaloids offer potential therapeutic agents against most of these disorders and amenable for further drug design.
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http://dx.doi.org/10.1016/j.ejphar.2020.173837DOI Listing
February 2021

Molecular Basis of Modulating Adenosine Receptors Activities.

Curr Pharm Des 2019 ;25(7):817-831

Centre For Drug Research, Universiti Sains Malaysia, 11800 Gelugor, Penang, Malaysia.

Modulating cellular processes through extracellular chemical stimuli is medicinally an attractive approach to control disease conditions. GPCRs are the most important group of transmembranal receptors that produce different patterns of activations using intracellular mediators (such as G-proteins and Beta-arrestins). Adenosine receptors (ARs) belong to GPCR class and are divided into A1AR, A2AAR, A2BAR and A3AR. ARs control different physiological activities thus considered valuable target to control neural, heart, inflammatory and other metabolic disorders. Targeting ARs using small molecules essentially works by binding orthosteric and/or allosteric sites of the receptors. Although targeting orthosteric site is considered typical to modulate receptor activity, allosteric sites provide better subtype selectivity, saturable modulation of activity and variable activation patterns. Each receptor exists in dynamical equilibrium between conformational ensembles. The equilibrium is affected by receptor interaction with other molecules. Changing the population of conformational ensembles of the receptor is the method by which orthosteric, allosteric and other cellular components control receptor signaling. Herein, the interactions of ARs with orthosteric, allosteric ligands as well as intracellular mediators are described. A quinary interaction model for the receptor is proposed and energy wells for major conformational ensembles are retrieved.
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http://dx.doi.org/10.2174/1381612825666190304122624DOI Listing
February 2020

Rate and extent of mitragynine and 7-hydroxymitragynine blood-brain barrier transport and their intra-brain distribution: the missing link in pharmacodynamic studies.

Addict Biol 2019 09 8;24(5):935-945. Epub 2018 Aug 8.

Translational PKPD Group, Associate Member of SciLife Lab, Department of Pharmaceutical Biosciences, Uppsala University, Sweden.

Mitragyna speciosa is reported to be beneficial for the management of chronic pain and opioid withdrawal in the evolving opioid epidemic. Data on the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, the active compounds of the plant, are still lacking and inconclusive. Here, we present for the first time the rate and the extent of mitragynine and 7-hydroxymitragynine transport across the BBB, with an investigation of their post-BBB intra-brain distribution. We utilized an in vitro BBB model to study the rate of BBB permeation of the compounds and their interaction with efflux transporter P-glycoprotein (P-gp). Mitragynine showed higher apical-to-basolateral (A-B, i.e. blood-to-brain side) permeability than 7-hydroxymitragynine. 7-Hydroxymitragynine showed a tendency to efflux, with efflux ratio (B-A/A-B) of 1.39. Both were found to inhibit the P-gp and are also subject to efflux by the P-gp. Assessment of the extent of BBB transport in vivo in rats from unbound brain to plasma concentration ratios (K ) revealed extensive efflux of both compounds, with less than 10 percent of unbound mitragynine and 7-hydroxymitragynine in plasma crossing the BBB. By contrast, the extent of intra-brain distribution was significantly different, with mitragynine having 18-fold higher brain tissue uptake in brain slice assay compared with 7-hydroxymitragynine. Mitragynine showed a moderate capacity to accumulate inside brain parenchymal cells, while 7-hydroxymitragynine showed restricted cellular barrier transport. The presented findings from this systematic investigation of brain pharmacokinetics of mitragynine and 7-hydroxymitragynine are essential for design and interpretation of in vivo experiments aiming to establish exposure-response relationship.
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http://dx.doi.org/10.1111/adb.12661DOI Listing
September 2019

Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study.

Molecules 2016 Nov 9;21(11). Epub 2016 Nov 9.

Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia.

This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure-activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by : BioSolveIT's LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC value (45.77 ± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.
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http://dx.doi.org/10.3390/molecules21111500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274529PMC
November 2016

Assembly of ligands interaction models for glutathione-S-transferases from Plasmodium falciparum, human and mouse using enzyme kinetics and molecular docking.

Comput Biol Chem 2016 10 25;64:237-249. Epub 2016 Jul 25.

Centre For Drug Research, Universiti Sains Malaysia. Gelugor 11700 Penang, Malaysia.

Background: Glutathione-s-transferases (GSTs) are enzymes that principally catalyze the conjugation of electrophilic compounds to the endogenous nucleophilic glutathione substrate, besides, they have other non-catalytic functions. The Plasmodium falciparum genome encodes a single isoform of GST (PfGST) which is involved in buffering the toxic heme, thus considered a potential anti-malarial target. In mammals several classes of GSTs are available, each of various isoforms. The human (human GST Pi-1 or hGSTP1) and mouse (murine GST Mu-1 or mGSTM1) GST isoforms control cellular apoptosis by interaction with signaling proteins, thus considered as potential anti-cancer targets. In the course of GSTs inhibitors development, the models of ligands interactions with GSTs are used to guide rational molecular modification. In the absence of X-ray crystallographic data, enzyme kinetics and molecular docking experiments can aid in addressing ligands binding modes to the enzymes.

Methods: Kinetic studies were used to investigate the interactions between the three GSTs and each of glutathione, 1-chloro-2,4-dinitrobenzene, cibacron blue, ethacrynic acid, S-hexyl glutathione, hemin and protoporphyrin IX. Since hemin displacement is intended for PfGST inhibitors, the interactions between hemin and other ligands at PfGST binding sites were studied kinetically. Computationally determined binding modes and energies were interlinked with the kinetic results to resolve enzymes-ligands interaction models at atomic level.

Results: The results showed that hemin and cibacron blue have different binding modes in the three GSTs. Hemin has two binding sites (A and B) with two binding modes at site-A depending on presence of GSH. None of the ligands were able to compete hemin binding to PfGST except ethacrynic acid. Besides bind differently in GSTs, the isolated anthraquinone moiety of cibacron blue is not maintaining sufficient interactions with GSTs to be used as a lead. Similarly, the ethacrynic acid uses water bridges to mediate interactions with GSTs and at least the conjugated form of EA is the true hemin inhibitor, thus EA may not be a suitable lead.

Conclusions: Glutathione analogues with bulky substitution at thiol of cysteine moiety or at γ-amino group of γ-glutamine moiety may be the most suitable to provide GST inhibitors with hemin competition.
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http://dx.doi.org/10.1016/j.compbiolchem.2016.07.007DOI Listing
October 2016

NMR structural assignments for four new 6-methoxy-tetrahydro-ß-carboline derivatives.

Magn Reson Chem 2015 Oct 1;53(10):857-9. Epub 2015 Jul 1.

Universiti Sains Malaysia, Centre for Drug Research, 11800, Minden, Pulau Pinang, Malaysia.

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http://dx.doi.org/10.1002/mrc.4273DOI Listing
October 2015

5-Methoxytryptamine reacts with natural food flavour to produce 6-methoxy tetrahydro-β-carbolines: in vitro investigation of their antioxidant and cytotoxicity properties.

Food Chem 2015 Sep 19;183:208-16. Epub 2015 Mar 19.

Centre for Drug Research, Universiti Sains Malaysia, Penang 11800, Malaysia. Electronic address:

Various 6-methoxytetrahydro-β-carboline derivatives, namely BEN (6-methoxy-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), ANI (6-methoxy-1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), ACE (6-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole) and VAN (2-methoxy-4-(6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-l)phenol), were prepared via the Maillard reaction using food flavours and 5-methoxytryptamine in aqueous medium and were investigated for their in vitro antioxidant and cytotoxicity properties. These derivatives were found to exhibit moderate antioxidant properties, based on a combination of DPPH, ABTS and FRAP assays. The results suggested that the Maillard reaction could be used to generate β-carboline antioxidants. It was beneficial that VAN showed the highest antioxidant activity but the least cytotoxic activities on non-tumourous cell lines of NIH/3T3, CCD18-Co and B98-5 using MTT assay. ACE, ANI and BEN showed mild toxicity at effective antioxidative concentrations derived from DPPH and ABTS assays. Furthermore, they are safer compared to 5-fluorouracil, cisplatin and betulinic acid on NIH/3T3, CCD18-Co and B98-5 cells. In conclusion, the antioxidant and cytotoxicity properties of 6-methoxytetrahydro-β-carbolines were demonstrated for the first time.
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http://dx.doi.org/10.1016/j.foodchem.2015.03.044DOI Listing
September 2015

Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue.

Asian Pac J Cancer Prev 2014 ;15(14):5659-65

Centre for Drug Research, Universiti Sains Malaysia, Penang, Malaysia E-mail :

Background: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro.

Materials And Methods: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively.

Results: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): 2.25±0.02 mmol trolox / mmol and 1.96±0.04 mmol trolox / mmol respectively) and DPPH (IC50=3.75±0.04 mg/mL and IC50=2.28±0.02 mg/mL respectively). Both MTG and SRM demonstrate equal potency (IC50=25.20±1.53 and IC50= 22.19±1.06 respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) (IC5024.40±1.26). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > 100 μM towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60).

Conclusions: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.
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June 2015

6-Meth-oxy-1-(4-meth-oxy-phen-yl)-1,2,3,4-tetra-hydro-9H-β-carbolin-2-ium acetate.

Acta Crystallogr Sect E Struct Rep Online 2012 May 21;68(Pt 5):o1483. Epub 2012 Apr 21.

In the title compound, C(19)H(21)N(2)O(2) (+)·C(2)H(3)O(2) (-), the 1H-indole ring system is essentially planar [maximum deviation = 0.0257 (14) Å] and forms a dihedral angle of 87.92 (7) Å with the benzene ring attached to the tetra-hydro-pyridinium fragment. The tetra-hydro-pyridinium ring adopts a half-chair conformation. In the crystal, cations and anions are linked by inter-ionic N-H⋯O, C-H⋯O and C-H⋯N hydrogen bonds into chains along the a axis.
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http://dx.doi.org/10.1107/S1600536812016753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344593PMC
May 2012

Bis(6-meth-oxy-1-methyl-2,3,4,9-tetra-hydro-1H-β-carbolin-2-ium) tetra-chloridozincate(II) dihydrate.

Acta Crystallogr Sect E Struct Rep Online 2012 Apr 24;68(Pt 4):m464-5. Epub 2012 Mar 24.

The asymmetric unit of the title compound, (C(13)H(17)N(2)O)(2)[ZnCl(4)]·2H(2)O, contains two tetra-hydro-harmine cations, one tetra-chloro-zincate(II) anion and two water mol-ecules. In the cations, the two 1H-indole ring systems are essentially planar, with maximum deviations of 0.016 (2) and 0.018 (2) Å, and both tetra-hydro-pyridinium rings show a half-chair conformation. The Zn(II) complex anion has a distorted tetra-hedral geometry. In the crystal, inter-molecular N-H⋯O, N-H⋯Cl, O-H⋯O, O-H⋯Cl and C-H⋯O hydrogen bonds link the components into a three-dimensional network. A π-π inter-action with a centroid-centroid distance of 3.542 (14) Å is also observed.
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http://dx.doi.org/10.1107/S1600536812011130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343857PMC
April 2012

Brine shrimp lethality and acute oral toxicity studies on Swietenia mahagoni (Linn.) Jacq. seed methanolic extract.

Pharmacognosy Res 2010 Jul;2(4):215-20

Center for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia.

Background: The seeds of Swietenia mahagoni have been applied in folk medicine for the treatment of hypertension, diabetes, malaria, amoebiasis, cough, chest pain, and intestinal parasitism. Here we are the first to report on the toxicity of the Swietenia mahagoni crude methanolic (SMCM) seed extract.

Methods: SMCM seed extract has been studied for its brine shrimp lethality and acute oral toxicity, in mice.

Results: The brine shrimp lethality bioassay shows a moderate cytotoxicity at high concentration. The LC50 for the extract is 0.68 mg/ml at 24 hours of exposure. The LD50 of the SMCM seed extract for acute oral toxicity in mice is greater than 5000 mg/kg.

Conclusion: This study demonstrates that Swietenia mahagoni crude methanolic seed extract may contain bioactive compounds of potential therapeutic significance which are relatively safe from toxic effects, and can compromise the medicinal use of this plant in folk medicine.
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http://dx.doi.org/10.4103/0974-8490.69107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141130PMC
July 2010

In vitro and in vivo effects of three different Mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes--glutathione transferases (GSTs).

Molecules 2010 Jan 20;15(1):432-41. Epub 2010 Jan 20.

Centre for Drug Research, Universiti Sains Malaysia, 11800 USM Penang, Malaysia.

In the present study, we investigate the effects of three different Mitragyna speciosa extracts, namely methanolic, aqueous and total alkaloid extracts, on glutathione transferase-specific activity in male Sprague Dawley rat liver cytosol in vitro and in vivo. In the in vitro study, the effect of Mitragyna speciosa extracts (0.01 to 750 microg/mL) against the specific activity of glutathione transferases was examined in rat liver cytosolic fraction from untreated rats. Our data show concentration dependent inhibition of cytosolic GSTs when Mitragyna speciosa extract was added into the reaction mixture. At the highest concentration used, the methanolic extract showed the highest GSTs specific activity inhibition (61%), followed by aqueous (50%) and total alkaloid extract (43%), respectively. In in vivo study, three different dosages; 50, 100 and 200 mg/kg for methanolic and aqueous extracts and 5, 10 and 20 mg/kg for total alkaloid extract were given orally for 14 days. An increase in GST specific activity was generally observed. However, only Mitragyna speciosa aqueous extract with a dosage of 100 mg/kg showed significant results: 129% compared to control.
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http://dx.doi.org/10.3390/molecules15010432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256986PMC
January 2010

In Vitro antioxidant and xanthine oxidase inhibitory activities of methanolic Swietenia mahagoni seed extracts.

Molecules 2009 Nov 6;14(11):4476-85. Epub 2009 Nov 6.

Centre for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia.

This study examines the in vitro antioxidant activities of the methanol extract of Swietenia mahagoni seeds (SMCM seed extract). The extract was screened for possible antioxidant activities by free radical scavenging activity (DPPH), xanthine oxidase inhibition (XOI), hydrogen peroxide scavenging activity (HPSA) and ferric-reducing antioxidant power (FRAP) assays. The total phenolic and flavonoid contents were also determined. The extract exhibits antioxidant activity of 23.29% with an IC(50 )value of 2.3 mg/mL in the DPPH radical scavenging method, 47.2% in the XOI assay, 49.5% by the HPSA method, and 0.728 mmol/Fe(II)g in the FRAP method at the concentration tested. The amount of total phenolics and flavonoid contents was 70.83 mg gallic acid equivalent (GAE) and 2.5 +/- 0.15 mg of catechin equivalent per gram of dry extract, respectively. High Performance Thin Layer Chromatography (HPTLC) screening indicates the presence of phenolic compounds in the SMCM seed extract. The results indicate that the extract has both high free radical scavenging and xanthine oxidase inhibition activity. The antioxidant activity of SMCM seed extract is comparable with that of other Malaysian tropical fruits and herbal plants.
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http://dx.doi.org/10.3390/molecules14114476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254912PMC
November 2009

Docking of sialic acid analogues against influenza A hemagglutinin: a correlational study between experimentally measured and computationally estimated affinities.

J Mol Model 2010 May 13;16(5):1047-58. Epub 2009 Nov 13.

Centre for Drug Research, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.

A molecular docking tool of AutoDock3.05 was evaluated for its ability to reproduce experimentally determined affinities of various sialic acid analogues toward hemagglutinin of influenza A virus. With the exception of those with a C6-modified glycerol side chain, the experimental binding affinities of most sialic acid analogues (C2, C4 and C5-substituted) determined by viral hemadsorption inhibition assay, hemagglutination inhibition assay and nuclear magnetic resonance correlated well with the computationally estimated free energy of binding. Sialic acid analogues with modified glycerol side chains showed only poor correlation between the experimentally determined hemagglutinin inhibitor affinities and AutoDock3.05 scores, suggesting high mobility of the glutamic acid side chain at the glycerol binding pocket, which is difficult to simulate using a flexi-rigid molecular docking approach. In conclusion, except for some glycerol-substituted sialic acid analogues, the results showed the effectiveness of AutoDock3.05 searching and scoring functions in estimating affinities of sialic acid analogues toward influenza A hemagglutinin, making it a reliable tool for screening a database of virtually designed sialic acid analogues for hemagglutinin inhibitors.
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http://dx.doi.org/10.1007/s00894-009-0618-7DOI Listing
May 2010

Site-directed fragment-based generation of virtual sialic acid databases against influenza A hemagglutinin.

J Mol Model 2010 May 25;16(5):975-91. Epub 2009 Oct 25.

Centre for Drug Research, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia.

In this study fragment-based drug design is combined with molecular docking simulation technique, to design databases of virtual sialic acid (SA) analogues with new substitutions at C2, C5 and C6 positions of SA scaffold. Using spaces occupied by C2, C5 and C6 natural moieties of SA when bound to hemagglutinin (HA) crystallographic structure, new fragments that are commercially available were docked independently in all the pockets. The oriented fragments were then connected to the SA scaffold with or without incorporation of linker molecules. The completed analogues were docked to the whole SA binding site to estimate their binding conformations and affinities, generating three databases of HA-bound SA analogues. Selected new analogues showed higher estimated affinities than the natural SA when tested against H3N2, H5N1 and H1N1 subtypes of influenza A. An improvement in the binding energies indicates that fragment-based drug design when combined with molecular docking simulation is capable to produce virtual analogues that can become lead compound candidates for anti-flu drug discovery program.
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http://dx.doi.org/10.1007/s00894-009-0606-yDOI Listing
May 2010
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