MyMedR

Benzimidazole derivatives as new α-glucosidase inhibitors and in silico studies

Zawawi NK, Taha M, Ahmat N, Wadood A, Ismail NH, Rahim F, et al.

Bioorg Chem, 2016 Feb;64:29-36.

PMID: 26637946 DOI: 10.1016/j.bioorg.2015.11.006

Newly synthesized benzimidazole hydrazone derivatives 1-26 were evaluated for their α-glucosidase inhibitory activity. Compounds 1-26 exhibited varying degrees of yeast α-glucosidase inhibitory activity with IC50 values between 8.40 ± 0.76 and 179.71 ± 1.11 μM when compared with standard acarbose. In this assay, seven compounds that showed highest inhibitory effects than the rest of benzimidazole series were identified. All the synthesized compounds were characterized by different spectroscopic methods adequately. We further evaluated the interaction of the active compounds with enzyme with the help of docking studies.

Fulltext Inhibitory effect of triterpenoids from Dillenia serrata (Dilleniaceae) on prostaglandin E2 production and quantitative HPLC analysis of its koetjapic acid and betulinic acid contents

Jalil J, Sabandar CW, Ahmat N, Jamal JA, Jantan I, Aladdin NA, et al.

Molecules, 2015 Feb 16;20(2):3206-20.

PMID: 25690285 DOI: 10.3390/molecules20023206

The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E2 (PGE2) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated from the root bark of the plant, koetjapic (1), 3-oxoolean-12-en-30-oic (2), and betulinic (3) acids, exhibited significant concentration-dependent inhibitory effects on PGE2 production with IC50 values of 1.05, 1.54, and 2.59 μM, respectively, as compared with the positive control, indomethacin (IC50 = 0.45 μM). Quantification of compounds 1 and 3 in the methanol extracts and fractions were carried out by using a validated reversed-phase high performance liquid chromatography (RP-HPLC) method. The ethyl acetate fraction of the stem bark showed the highest content of both compound 1 (15.1%) and compound 3 (52.8%). The strong inhibition of the extracts and fractions on cyclooxygenase-2 (COX-2) enzymatic activity was due to the presence of their major constituents, especially koetjapic and betulinic acids.

A new triterpenoid from Sapium baccatum (Euphorbiaceae)

Al Muqarrabun LM, Ahmat N, Aris SR, Norizan N, Shamsulrijal N, Yusof FZ, et al.

Nat Prod Res, 2014;28(13):1003-9.

PMID: 24697194 DOI: 10.1080/14786419.2014.903396

A new triterpene, malaytaraxerate (1), and four known compounds, taraxerol (2), taraxerone (3), docosyl isoferulate (4) and docosanoic acid 2',3'-dihydroxypropyl ester (5), were isolated from the acetone extract of Sapium baccatum stem bark. The structures of the isolated compounds were determined using several spectroscopic methods, including UV-Vis, FT-IR, 1D and 2D NMR, and mass spectrometry. Major isolated compounds were assayed for cytotoxicity. The chemotaxonomic significance of this plant was also studied.

A new sesquiterpenoid from Scaphium macropodum (Miq.) Beumee

Al Muqarrabun LM, Ahmat N, Aris SR, Shamsulrijal N, Baharum SN, Ahmad R, et al.

Nat Prod Res, 2014;28(9):597-605.

PMID: 24568340 DOI: 10.1080/14786419.2014.886211

A new sesquiterpenoid, malayscaphiol (1), and three known compounds, lupeol (2), lupenone (3) and stigmasterol (4), were isolated from the methanolic extract of the stem bark of Scaphium macropodum. The structures of the isolated compounds were determined using several spectroscopic methods, including UV-vis, FT-IR, 1D and 2D NMR, and mass spectrometer. Major isolated compounds were assayed for cytotoxicity and anti-acetylcholinesterase activities. The chemotaxonomy significance of this plant was also discussed.

A study on the use of abbreviations among doctors and nurses in the medical department of a tertiary hospital in Malaysia

Koh KC, Lau KM, Yusof SA, Mohamad AI, Shahabuddin FS, Ahmat NH, et al.

Med J Malaysia, 2015 Dec;70(6):334-40.

PMID: 26988205 MyJurnal

INTRODUCTION: Misinterpretation of abbreviations by healthcare professionals has been reported to compromise patient safety. This study was done to determine the prevalence of abbreviations usage among medical doctors and nurses and their ability to interpret commonly used abbreviations in medical practice.

METHODS: Seventy-seven medical doctors and eighty nurses answered a self-administered questionnaire designed to capture demographic data and information regarding abbreviation use in medical practice. Comparisons were made between doctors and nurses with regards to frequency and reasons for using abbreviations; from where abbreviations were learned; frequency of encountering abbreviations in medical practice; prevalence of medical errors due to misinterpretation of abbreviations; and their ability to correctly interpret commonly used abbreviations.

RESULTS: The use of abbreviations was highly prevalent among doctors and nurses. Time saving, avoidance of writing sentences in full and convenience, were the main reasons for using abbreviations. Doctors learned abbreviations from fellow doctors while nurses learned from fellow nurses and doctors. More doctors than nurses reported encountering abbreviations. Both groups reported no difficulties in interpreting abbreviations although nurses reported often resorting to guesswork. Both groups felt abbreviations were necessary and an acceptable part of work. Doctors outperformed nurses in correctly interpreting commonly used standard and non-standard abbreviations.

CONCLUSION: The use of standard and non-standard abbreviation in clinical practice by doctors and nurses was highly prevalent. Significant variability in interpretation of abbreviations exists between doctors and nurses.

Novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone: a new class of β-glucuronidase inhibitors and in silico studies

Zawawi NK, Taha M, Ahmat N, Wadood A, Ismail NH, Rahim F, et al.

Bioorg Med Chem, 2015 Jul 1;23(13):3119-25.

PMID: 26001340 DOI: 10.1016/j.bmc.2015.04.081

A library of novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone (3a-3r) was synthesized and evaluated for their potential as β-glucuronidase inhibitors. Several compounds such as 3a-3d, 3e-3j, 3l-3o, 3q and 3r showed excellent inhibitory potentials much better than the standard (IC50=48.4±1.25μM: d-saccharic acid 1,4-lactone). All the synthesized compounds were characterized satisfactorily by using different spectroscopic methods. We further evaluated the interaction of the active compounds and the enzyme active site with the help of docking studies.

Benzimidazole derivatives protect against cytokine-induced apoptosis in pancreatic β-Cells

Zawawi NK, Rajput SA, Taha M, Ahmat N, Ismail NH, Abdullah N, et al.

Bioorg Med Chem Lett, 2015 Oct 15;25(20):4672-6.

PMID: 26330080 DOI: 10.1016/j.bmcl.2015.08.022

Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimidazole derivatives, capable of rescuing pancreatic β-cells from cytokine-induced apoptosis. Three hydrazone derivatives of benzimidazole significantly increased the cellular ATP levels, reduced caspase-3 activity, reduced nitrite production and increased glucose-stimulated insulin secretion in the presence of proinflammatory cytokines. These findings suggest that these compounds may protect β-cells from the harmful effects of cytokines and may serve as candidates for therapeutic intervention for diabetes.

Synthesis of novel disulfide and sulfone hybrid scaffolds as potent β-glucuronidase inhibitor

Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Al Muqarrabin LM, et al.

Bioorg Chem, 2016 10;68:15-22.

PMID: 27414468 DOI: 10.1016/j.bioorg.2016.07.002

Novel series of disulfide and sulfone hybrid analogs (1-20) were synthesized and characterized through EI-MS and (1)H NMR and evaluated for β-glucuronidase inhibitory potential. All synthesized analogs except 13 and 15 showed excellent β-glucuronidase inhibitory potential with IC50 value ranging in between 2.20-88.16μM as compared to standard d-saccharic acid 1,4 lactone (48.4±1.25μM). Analogs 19, 16, 4, 1, 17, 6, 10, 3, 18, 2, 11, 14 and 5 showed many fold potent activity against β-glucuronidase inhibitor. Structure activity relationship showed that substitution of electron withdrawing groups at ortho as well as para position on phenyl ring increase potency. Electron withdrawing groups at meta position on phenyl ring showed slightly low potency as compared to ortho and para position. The binding interactions were confirmed through molecular docking studies.

Synthesis of Bis-indolylmethane sulfonohydrazides derivatives as potent α-Glucosidase inhibitors

Gollapalli M, Taha M, Ullah H, Nawaz M, AlMuqarrabun LMR, Rahim F, et al.

Bioorg Chem, 2018 10;80:112-120.

PMID: 29894890 DOI: 10.1016/j.bioorg.2018.06.001

In search of better α-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their α-glucosidase inhibitory potential. All derivatives exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 0.10 ± 0.05 to 5.1 ± 0.05 μM when compared with standard drug acarbose having IC50 value 856.28 ± 3.15 μM. Among the series, analog 7 (0.10 ± 0.05 μM) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of α-glucosidase (∼ 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of α-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic.

Induction of apoptosis and G2/M arrest by ampelopsin E from Dryobalanops towards triple negative breast cancer cells, MDA-MB-231

Rahman NA, Yazan LS, Wibowo A, Ahmat N, Foo JB, Tor YS, et al.

BMC Complement Altern Med, 2016;16:354.

PMID: 27609190 DOI: 10.1186/s12906-016-1328-1

Several compounds isolated from Dryobalanops have been reported to exhibit cytotoxic effects to several cancer cell lines. This study investigated the cytotoxic effects, cell cycle arrest and mode of cell death in ampelopsin E-treated triple negative cells, MDA-MB-231.

Bisindolylmethane thiosemicarbazides as potential inhibitors of urease: Synthesis and molecular modeling studies

Taha M, Ullah H, Al Muqarrabun LMR, Khan MN, Rahim F, Ahmat N, et al.

Bioorg Med Chem, 2018 01 01;26(1):152-160.

PMID: 29183662 DOI: 10.1016/j.bmc.2017.11.028

Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14 ± 0.01 to 18.50 ± 0.90 μM when compared with the standard inhibitor thiourea having IC50 value 21.25 ± 0.90 μM. Among the series, analog 9 (0.14 ± 0.01 μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.

Fulltext Synthesis, crystal structure, DFT studies and evaluation of the antioxidant activity of 3,4-dimethoxybenzenamine schiff bases

Aziz AN, Taha M, Ismail NH, Anouar el H, Yousuf S, Jamil W, et al.

Molecules, 2014 Jun 19;19(6):8414-33.

PMID: 24950444 DOI: 10.3390/molecules19068414

Schiff bases of 3,4-dimethoxybenzenamine 1-25 were synthesized and evaluated for their antioxidant activity. All the synthesized compounds were characterized by various spectroscopic techniques. In addition, the characterizations of compounds 13, 15 and 16 were supported by crystal X-ray determinations and their geometrical parameters were compared with theoretical DFT calculations at the B3LYP level of theory. Furthermore, the X-ray crystal data of two non-crystalline compounds 8 and 18 were theoretically calculated and compared with the practical values of compounds 13, 15, 16 and found a good agreement. The compounds showed good DPPH scavenging activity ranging from 10.12 to 84.34 μM where compounds 1-4 and 6 showed stronger activity than the standard n-propyl gallate. For the superoxide anion radical assay, compounds 1-3 showed better activity than the standard.

A new symmetrical tetramer oligostilbenoid containing tetrahydrofuran ring from the stem bark of Dryobalanops lanceolata

Ahmat N, Wibowo A, Mohamad SA, Low AL, Sufian AS, Yusof MI, et al.

J Asian Nat Prod Res, 2014;16(11):1099-107.

PMID: 25034352 DOI: 10.1080/10286020.2014.938059

A new tetramer oligostilbenoid possessing tetrahydrofuran ring, malaysianol C (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata, together with four known oligostilbenoids nepalensinol E (2), ϵ-viniferin (3), laevifonol (4), and ampelopsin F (5). The structures of isolated compounds were elucidated on the basis of spectral evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay, whereas the cytotoxic activity was tested using MTT assay. The plausible biogenetic routes of the isolated compounds are also discussed.

Medicinal uses, phytochemistry and pharmacology of Pongamia pinnata (L.) Pierre: a review

Al Muqarrabun LM, Ahmat N, Ruzaina SA, Ismail NH, Sahidin I

J Ethnopharmacol, 2013 Nov 25;150(2):395-420.

PMID: 24016802 DOI: 10.1016/j.jep.2013.08.041

Pongamia pinnata (L.) Pierre is one of the many plants with diverse medicinal properties where all its parts have been used as traditional medicine in the treatment and prevention of several kinds of ailments in many countries such as for treatment of piles, skin diseases, and wounds.

Bioactive oligostilbenoids from Shorea maxwelliana King and their chemotaxonomic significance

Zawawi NK, Ahmat N, Mazatulikhma MZ, Shafiq RM, Wahid NH, Sufian AS

Nat Prod Res, 2013;27(17):1589-93.

PMID: 23035830 DOI: 10.1080/14786419.2012.730047

Phytochemical investigation on the stem bark of Shorea maxwelliana yielded five oligostilbenoids identified as α-viniferin (1), maximol A (2), vaticanol A (3), suffruticosol A (4) and vaticanol G (5). Chemotaxonomy of isolated compounds was discussed briefly. Major compounds were tested for neurotoxic and cytotoxic activities. Neurotoxicity for all tested compounds did not pose any toxic effect against cultured cell (cell viability range ±100-94%). Compounds 2-5 possessed active cyctotoxic activity against HL60 cell line with IC50 values range of 2.7-78 µg mL(-1).

Malaysianol B, an oligostilbenoid derivative from Dryobalanops lanceolata

Wibowo A, Ahmat N, Hamzah AS, Low AL, Mohamad SA, Khong HY, et al.

Fitoterapia, 2012 Dec;83(8):1569-75.

PMID: 22982329 DOI: 10.1016/j.fitote.2012.09.004

A new oligostilbenoid tetramer, malaysianol B (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata along with seven oligostilbenoids tetramers; hopeaphenol (2), stenophyllol A (3), nepalensinol B (4), vaticanol B (5) and C (6), upunaphenol D (7), and flexuosol A (8). The structures of the isolated compounds were established on the basis of their spectroscopic data evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay.

Fulltext Anthraquinones with antiplasmodial activity from the roots of Rennellia elliptica Korth. (Rubiaceae)

Osman CP, Ismail NH, Ahmad R, Ahmat N, Awang K, Jaafar FM

Molecules, 2010;15(10):7218-26.

PMID: 20966871 DOI: 10.3390/molecules15107218

Dichloromethane root extract of Rennellia elliptica Korth. showed strong inhibition of Plasmodium falciparum growth in vitro with an IC₅₀ value of 4.04 µg/mL. A phytochemical study of the dichloromethane root extract has led to the isolation and characterization of a new anthraquinone, 1,2-dimethoxy-6-methyl-9,10-anthraquinone (1), and ten known anthraquinones: 1-hydroxy-2-methoxy-6-methyl-9,10-anthraquinone (2), nordamnacanthal (3), 2-formyl-3-hydroxy-9,10-anthraquinone (4), damnacanthal (5), lucidin-ω-methyl ether (6), 3-hydroxy-2-methyl-9,10-anthraquinone (7), rubiadin (8), 3-hydroxy-2-methoxy-6-methyl-9,10-anthraquinone (9), rubiadin-1-methyl ether (10) and 3-hydroxy-2-hydroxymethyl-9,10-anthraquinone (11). Structural elucidation of all compounds was accomplished by modern spectroscopic methods, notably 1D and 2D NMR, IR, UV and HREIMS. The new anthraquinone 1, 2-formyl-3-hydroxy-9,10-anthraquinone (4) and 3-hydroxy-2-methyl-9,10-anthraquinone (7) possess strong antiplasmodial activity, with IC₅₀ values of 1.10, 0.63 and 0.34 µM, respectively.

Malaysianol A, a new trimer resveratrol oligomer from the stem bark of Dryobalanops aromatica

Wibowo A, Ahmat N, Hamzah AS, Sufian AS, Ismail NH, Ahmad R, et al.

Fitoterapia, 2011 Jun;82(4):676-81.

PMID: 21338657 DOI: 10.1016/j.fitote.2011.02.006

A new resveratrol trimer, malaysianol A (1), five known resveratrol oligomers: laevifonol (2), ampelopsin E (3), α-viniferin (4), ε-viniferin (5), diptoindonesin A (6), and bergenin (7) have been isolated from the acetone extract of the stem bark of Dryobalanops aromatica by combination of vacuum and radial chromatography techniques. Their structures were established on the basis of their spectroscopic evidence and comparison with the published data. The cytotoxic activity of the compounds was tested against several cell lines in which compound 4 was found to inhibit strongly the growth of HL-60 cell line.

Isolation and identification of antibacterial and cytotoxic compounds from the leaves of Muntingia calabura L

Sufian AS, Ramasamy K, Ahmat N, Zakaria ZA, Yusof MI

J Ethnopharmacol, 2013 Mar 7;146(1):198-204.

PMID: 23276785 DOI: 10.1016/j.jep.2012.12.032

Muntingia calabura (Elaeocarpaceae) is one of the most common roadside trees in Malaysia. Its leaves, barks, flowers and roots have been used as a folk remedy for the treatment of fever, incipient cold, liver disease, as well as an antiseptic agent in Southeast Asia. The aim of this study is to isolate and identify the antibacterial and cytotoxic compounds from the leaves of Muntingia calabura L.

Synthesis, in vitro evaluation and molecular docking studies of biscoumarin thiourea as a new inhibitor of α-glucosidases

Zawawi NK, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F, et al.

Bioorg Chem, 2015 Dec;63:36-44.

PMID: 26432614 DOI: 10.1016/j.bioorg.2015.09.004

Biscoumarin analogs 1-18 have been synthesized, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All compounds showed variety of α-glucosidase inhibitory potential ranging in between 13.5±0.39 and 104.62±0.3μM when compared with standard acarbose having IC50 value 774.5±1.94μM. The binding interactions of the most active analogs were confirmed through molecular docking. The compounds showed very good interactions with enzyme. All synthesized compounds 1-18 are new. Our synthesized compounds can further be studied to developed lead compounds.

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