MyMedR

Awang K, Mukhtar MR, Mustafa MR, Litaudon M, Shaari K, Mohamad K, et al.

Nat Prod Res, 2007 Jul 10;21(8):704-9.

The leaves of the Phoebe scortechinii (Gamb.) Kochummen Comb. Nov. (Lauraceae), afforded one new proaporphine-tryptamine dimer; (-)-phoebescortechiniine (1), along with two known ones; phoebegrandine A and phoebegrandine B. The proaporphine, tetrahydropronuciferine (2), was isolated for the first time as a natural product. The alkaloids were elucidated primarily by means of high field NMR and HRMS.

Fulltext 17-(5-Ethyl-6-methyl-heptan-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-deca-hydro-1H-cyclo-penta[a]phenanthrene-3,7-diol from Chisocheton tomentosus (Meliaceae)

Najmuldeen IA, Hadi AH, Awang K, Mohamad K, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2008;64(Pt 11):o2163.

PMID: 21581023 DOI: 10.1107/S1600536808033163

The asymmetric unit of the title compound, C(29)H(50)O(2), contains two mol-ecules; one mol-ecule is linked to the other by two O-H⋯O hydrogen bonds, whereas only one of the hydr-oxy groups of the second mol-ecule is involved in hydrogen bonding. This gives rise to a chain that runs along the a axis of the monoclinic unit cell.

Erythrocarpines A-E, new cytotoxic limonoids from Chisocheton erythrocarpus

Awang K, Lim CS, Mohamad K, Morita H, Hirasawa Y, Takeya K, et al.

Bioorg Med Chem, 2007 Sep 1;15(17):5997-6002.

PMID: 17576066

Five new cytotoxic limonoids, erythrocarpines A-E (1-5), were isolated from the bark of Chisocheton erythrocarpus Hiern. Chemical structures, stereochemistry, and conformation were fully elucidated and characterized by 2D NMR, MS, and computational methods.

Fulltext Prevalence and Factors Influencing Visual Memory Dysfunction among Epilepsy Patients-A Single-Center Study

Beh HC, Tan HJ, Hod R, Khoo CS, Mohamad K

Neurol India, 2020 7 10;68(3):581-585.

PMID: 32643667 DOI: 10.4103/0028-3886.289011

Background: Epilepsy is associated with cognitive impairment due to the disease itself or side-effects of antiepileptic drugs.

Objective: We aimed to study the prevalence of visual memory dysfunction among epilepsy patients and identify the predictors that could contribute to the impairment.

Materials and Methods: This was a cross-sectional study. We analyzed 250 patients with epilepsy from neurology clinic at our tertiary center. Assessment of visual memory was done using Wechsler Memory Scale-IV (WMS-IV) with scores from subsets of visual reproduction I, II and designs I, II contributing to visual memory index (VMI) score. The correlation between continuous variables was analyzed using Pearson correlation; whereas the VMI scores of different factors were analyzed via a 1-way ANOVA test. The statistical significance was set at P < 0.05.

Results: The prevalence of visual memory dysfunction in our epilepsy population was 37.2%. Analysis of individual predictors showed that older patients, lower educational level, combined generalized and focal types of epilepsy, longer duration of epilepsy, greater number of antiepileptic drugs (AEDs) used, and abnormal neuroimaging contributed to poor visual memory. Multiple logistic regression analysis showed that educational level, types of epilepsy, and the number of AEDs used were significant predictors for visual memory impairment.

Conclusion: Visual memory dysfunction in patients with epilepsy was due to manifold confounding factors. Our findings enabled us to identify patients with visual memory dysfunction and modifiable factors that contribute to it. WMS-IV is a suitable assessment tool to determine visual memory function, which can help clinicians to optimize the patients' treatment.

Fulltext Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment

Samat NA, Abdul Murad NA, Mohamad K, Abdul Razak MR, Mohamed Ibrahim N

Front Neurosci, 2017;11:712.

PMID: 29326545 DOI: 10.3389/fnins.2017.00712

Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15-20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E (ApoE) have been associated with the presence of cognitive impairment in PD although data have been inconsistent. Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms. Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGELAPoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol. Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA (p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. TheApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction (p = 0.014). Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.

Fulltext Regulation of apoptotic effects by erythrocarpine E, a cytotoxic limonoid from Chisocheton erythrocarpus in HSC-4 human oral cancer cells

Nagoor NH, Shah Jehan Muttiah N, Lim CS, In LL, Mohamad K, Awang K

PLoS One, 2011;6(8):e23661.

PMID: 21858194 DOI: 10.1371/journal.pone.0023661

The aim of this study was to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a limonoid extracted from Chisocheton erythrocarpus on human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a time and dose dependent manner with an IC(50) value of 4.0±1.9 µM within 24 h of treatment. CEB4 was also found to have minimal cytotoxic effects on the normal cell line, NHBE with cell viability levels maintained above 80% upon treatment. Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation assay results showed that CEB4 induces apoptosis mediated cell death. Western blotting results demonstrated that the induction of apoptosis by CEB4 appeared to be mediated through regulation of the p53 signalling pathway as there was an increase in p53 phosphorylation levels. CEB4 was also found to up-regulate the pro-apoptotic protein, Bax, while down-regulating the anti-apoptotic protein, Bcl-2, suggesting the involvement of the intrinsic mitochondrial pathway. Reduced levels of initiator procaspase-9 and executioner caspase-3 zymogen were also observed following CEB4 exposure, hence indicating the involvement of cytochrome c mediated apoptosis. These results demonstrate the cytotoxic and apoptotic ability of erythrocarpine E, and suggest its potential development as a cancer chemopreventive agent.

7α-Hydroxy-β-Sitosterol from Chisocheton tomentosus Induces Apoptosis via Dysregulation of Cellular Bax/Bcl-2 Ratio and Cell Cycle Arrest by Downregulating ERK1/2 Activation

Tasyriq M, Najmuldeen IA, In LL, Mohamad K, Awang K, Hasima N

Evid Based Complement Alternat Med, 2012;2012:765316.

PMID: 22997533

In continuation of our interest towards the elucidation of apoptotic pathways of cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects of 7α-hydroxy-β-sitosterol (CT1), a rare natural phytosterol oxide isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three different human tumor cell lines with minimal effects on normal cell controls, where cell viability levels were maintained ≥80% upon treatment. Our results showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1 was also found to increase proapoptotic Bax protein levels, while decreasing anti-apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3 were also observed following CT1 exposure, confirming the involvement of cytochrome c-mediated apoptosis via the mitochondrial pathway. These results demonstrated the cytotoxic and apoptotic ability of 7α-hydroxy-β-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.

Fulltext Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways

Looi CY, Moharram B, Paydar M, Wong YL, Leong KH, Mohamad K, et al.

BMC Complement Altern Med, 2013;13:166.

PMID: 23837445 DOI: 10.1186/1472-6882-13-166

Centratherum anthelminticum (L.) Kuntze (scientific synonyms: Vernonia anthelmintica; black cumin) is one of the ingredients of an Ayurvedic preparation, called "Kayakalp", commonly applied to treat skin disorders in India and Southeast Asia. Despite its well known anti-inflammatory property on skin diseases, the anti-cancer effect of C. anthelminticum seeds on skin cancer is less documented. The present study aims to investigate the anti-cancer effect of Centratherum anthelminticum (L.) seeds chloroform fraction (CACF) on human melanoma cells and to elucidate the molecular mechanism involved.

Fulltext Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds

Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, et al.

PLoS One, 2013;8(2):e56643.

PMID: 23437193 DOI: 10.1371/journal.pone.0056643

Centratherum anthelminticum (L.) seeds (CA) is a well known medicinal herb in Indian sub-continent. We recently reported anti-oxidant property of chloroform fraction of Centratherum anthelminticum (L.) seeds (CACF) by inhibiting tumor necrosis factor-α (TNF-α)-induced growth of human breast cancer cells. However, the active compounds in CACF have not been investigated previously.

Pseuduvarines A and B, two new cytotoxic dioxoaporphine alkaloids from Pseuduvaria rugosa

Taha H, Hadi AH, Nordin N, Najmuldeen IA, Mohamad K, Shirota O, et al.

Chem Pharm Bull (Tokyo), 2011;59(7):896-7.

PMID: 21720044

Pseuduvarines A (1) and B (2), two new dioxoaporphine alkaloids with an amino moiety, were isolated from the stem bark of Pseuduvaria rugosa and their structures were elucidated by combination of 2D-NMR spectroscopic analysis. Pseuduvarines A (1) and B (2) showed cytotoxicity against MCF7, HepG2, and HL-60 (1: IC₅₀, 0.9, 21.7, and >50.0 µM, respectively, 2: IC₅₀ >50.0, 15.7, and 12.4 µM, respectively).

Oppositinines A and B: new vasorelaxant beta-carboline alkaloids from Neisosperma oppositifolia

Ahmad K, Thomas NF, Hadi AH, Mukhtar MR, Mohamad K, Nafiah MA, et al.

Chem Pharm Bull (Tokyo), 2010 Aug;58(8):1085-7.

PMID: 20686264

A phytochemical study on the bark of Neisosperma oppositifolia (Apocynaceae) yielded two new beta-carboline indole alkaloids, oppositinines A (1) and B (2), together with five known alkaloids, isoreserpiline, isocarapanaubine, vobasine, 10-methoxydihydrocorynantheol-N-oxide, and ochropposinine oxindole. Structural elucidation of 1 and 2 was performed using 2D NMR methods. Oppositinines A (1) and B (2) showed potent vasorelaxant effects on the rat aorta.

Spectaflavoside A, a new potent iron chelating dimeric flavonol glycoside from the rhizomes of Zingiber spectabile Griff

Sivasothy Y, Hadi AH, Mohamad K, Leong KH, Ibrahim H, Sulaiman SF, et al.

Bioorg Med Chem Lett, 2012 Jun 1;22(11):3831-6.

PMID: 22546674 DOI: 10.1016/j.bmcl.2012.02.064

The rhizomes of Zingiber spectabile yielded a new dimeric flavonol glycoside for which the name kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside-(I-6,II-8)-kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside; spectaflavoside A (1) was proposed, along with kaempferol and its four acetylrhamnosides (2-6), demethoxycurcumin (7) and curcumin (8). The structure of spectaflavoside A was elucidated by spectroscopic methods including, 1D and 2D NMR techniques. This is the first report on the occurrence of a dimeric flavonol glycoside in the Zingiberaceae and the second in nature. Spectaflavoside A was found to be a potent iron chelating agent.

Fulltext Design, synthesis and cytotoxic evaluation of o-carboxamido stilbene analogues

Azmi MN, Din MF, Kee CH, Suhaimi M, Ping AK, Ahmad K, et al.

Int J Mol Sci, 2013;14(12):23369-89.

PMID: 24287912 DOI: 10.3390/ijms141223369

Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50=16.68 µM), colon cancer HT-29 (IC50=7.51 µM) and breast cancer MCF-7 (IC50=21.24 µM), respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.

Fulltext Kingianic acids A-G, Endiandric acid analogues from Endiandra kingiana

Azmi MN, Gény C, Leverrier A, Litaudon M, Dumontet V, Birlirakis N, et al.

Molecules, 2014;19(2):1732-47.

PMID: 24492595 DOI: 10.3390/molecules19021732

A phytochemical investigation of the methanolic extract of the bark of Endiandra kingiana led to the isolation of seven new tetracyclic endiandric acid analogues, kingianic acids A-G (1-7), together with endiandric acid M (8), tsangibeilin B (9) and endiandric acid (10). Their structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The structure of compounds 9 and 10 were confirmed by single-crystal X-ray diffraction analysis. These compounds were screened for Bcl-xL and Mcl-1 binding affinities and cytotoxic activity on various cancer cell lines. Compound 5 showed moderate cytotoxic activity against human colorectal adeno-carcinoma (HT-29) and lung adenocarcinoma epithelial (A549) cell lines, with IC50 values in the range 15-17 µM, and compounds 3, 6 and 9 exhibited weak binding affinity for the anti-apoptotic protein Mcl-1.

Neolamarckines A and B, new indole alkaloids from Neolamarckia cadamba

Qureshi AK, Mukhtar MR, Hirasawa Y, Hosoya T, Nugroho AE, Morita H, et al.

Chem Pharm Bull (Tokyo), 2011;59(2):291-3.

PMID: 21297315

Two new indole alkaloids, neolamarckines A and B (1, 2) were isolated from the leaves of Neolamarckia cadamba (Rubiaceae). Structural elucidation of 1 and 2 was performed by combination of 2D-NMR and circular dichroism (CD) spectra, and chemical correlations. Neolamarckine A (1) showed inhibition of inducible nitric oxide synthase (iNOS) dose dependently.

Fulltext Cytotoxic and antioxidant compounds from the stem bark of Goniothalamus tapisoides Mat Salleh

Kim RP, Bihud V, Bin Mohamad K, Leong KH, Bin Mohamad J, Bin Ahmad F, et al.

Molecules, 2012 Dec 21;18(1):128-39.

PMID: 23344192 DOI: 10.3390/molecules18010128

Eleven compounds:goniomicin A (1), goniomicin B (2), goniomicin C (3), goniomicin D (4), tapisoidin (5), goniothalamin (6), 9-deoxygoniopypyrone (7), pterodondiol (8), liriodenine (9), benzamide (10) and cinnamic acid (11), were isolated from the stem bark of Goniothalamus tapisoides. All compounds were identified by spectroscopic analysis and, for known compounds, by comparison with published data. Goniothalamin (6) exhibited mild cytotoxic activity towards a colon cancer cell line (HT-29), with an IC(50)value of 64.17 ± 5.60 µM. Goniomicin B (2) give the highest antioxidant activity in the DPPH assay among all compounds tested, with an IC(50) of 0.207 µM.

Chisomicines A-C, limonoids from Chisocheton ceramicus

Najmuldeen IA, Hadi AH, Awang K, Mohamad K, Ketuly KA, Mukhtar MR, et al.

J Nat Prod, 2011 May 27;74(5):1313-7.

PMID: 21428417 DOI: 10.1021/np200013g

Three new limonoids, chisomicines A-C (1-3), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.

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