Mohamad N., Phua Y.H., Abu Bakar M.H., Che Omar M.T., Wahab H.A., Supratman U., Awang K., Azmi M.N.
School of Chemical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia; Bioproces Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia; Biological Section, School of Distance Education, Universiti Sains Malaysia, Minden, Pulau Pinang 11800, Malaysia; School of Pharmaceutical Science, Universiti Sains Malaysia, Minden, Pulau Pinang 11800, Malaysia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas PadjadjaranBandung 45363, Indonesia; Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, 50603, Malaysia
A new series of ortho-carboxamidostilbenes derivatives were synthesized via Heck Coupling and screened for their α-amylase and α-glucosidase inhibitory potential. The results indicated that all the synthesized compounds showed a substantial α-glucosidase inhibitory potential (IC50 between 3-78 µg/mL) compared to acarbose (IC50 = 16.14 ± 1.05 µg/mL) as the standard. In addition, the IC50 values against α-amylase varying from 3-300 µg/mL when compared to a standard drug acarbose (IC50 = 21.12 ± 0.29 µg/mL). In silico studies were carried out to understand the binding interaction between active compounds and enzymes. The results indicated that the binding energy displayed by compound 5a-5e ranging from -7.9 to -9.0 and -7.2 to -8.5 kcal/mol for the C-terminal subunit of human maltase glucoamylase, ctMGAM (α-glucosidase) and α-amylase, respectively. The interaction modes of 5d (IC50 = 2.90 ± 0.58 µg/mL) in ctMGAM, showed that alkyl and methoxy group interacted with TRP1369 via hydrogen bond and hydrophobic interaction, respectively. Meanwhile, the interaction modes of 5e with (IC50 = 2.94 ± 0.69 µg/mL) in α-amylase showed that the methoxy group interacted with TYR151 via conventional hydrogen bond. These compounds may be considered promising candidates for the development of new anti-diabetic agents. © 2021 Elsevier B.V.
Heck coupling; molecular docking; ortho-carboxamidostilbenes; α-amylase; α-glucosidase
Journal of Molecular Structure
Publisher: Elsevier B.V.
Volume 1245, Issue , Art No 131007, Page – , Page Count
Journal Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85110301413&doi=10.1016%2fj.molstruc.2021.131007&partnerID=40&md5=49aae0c927598daa5effa63439ac1d11
Chen, Y., Li, P., Li, P., Yan, R., X. Zhang, Y. Wang, X. Zhang, W. Ye, Q. Zhang, α-glucosidase inhibitory effect and simultaneous quantification of three major flavonoid glycosides in Microctis folium (2013) Molecules, 18, pp. 4221-4232; Association, A.D., Classification and diagnosis of diabetes: Standards of medical care in diabetes (2019) Diabetes Care, 42, pp. S13-S28; Aune, D., Norat, T., Leitzmann, M., Tonstad, S., Vatten, L.J., Physical activity and the risk of type 2 diabetes: A systematic review and dose-response meta-analysis (2015) Eur. J. Epidemiol., 30, pp. 529-542; Holman, R.R., Cull, C.A., Turner, R.C., A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44) (1999) Diabetes Care, 22, pp. 960-964; Mahmood, N., A review of α-amylase inhibitors on weight loss and glycemic control in pathological state such as obesity and diabetes (2016) Comp. Clin. Path., 25, pp. 1253-1264; Obiro, W.C., Zhang, T., Jiang, B., The nutraceutical role of the Phaseolus vulgaris α-amylase inhibitor (2008) Br. J. Nutr., 100. , 1–1; Briguglio, G., Costa, C., Pollicino, M., Giambò, F., Catania, S., Fenga, C., (2020), pp. 1-11. , Polyphenols in cancer prevention: New insights (Review), Int. J. Funct. Nutr. 1; Ferrières, J., The French paradox: Lessons for other countries (2004) Heart, 90, pp. 107-111; Catalgol, B., Batirel, S., Taga, Y., Ozer, N.K., Resveratrol: French paradox revisited (2012) Front. Pharmacol., 3, pp. 1-18; Wang, B., Liu, T., Wu, Z., Zhang, L., Sun, J., Wang, X., Synthesis and biological evaluation of stilbene derivatives coupled to NO donors as potential antidiabetic agents (2018) J. Enzyme Inhib. Med. Chem., 33, pp. 416-423; Azmi, M.N., Md Din, M.F., Kee, C.H., Suhaimi, M., Ping, A.K., Ahmad, K., Nafiah, M.A., Awang, K., Design, synthesis and cytotoxicity evaluation of o-carboxamido stilbene analogues (2013) Int. J. Mol. Sci., 14, pp. 23369-23389; Abu Bakar, M.H., Lee, P.Y., Azmi, M.N., Syifa’ Lotfiamir, N., Mohamad, M.S.F., Shahril, N.S.N., Shariff, K.A., Litaudon, M., In vitro anti-hyperglycemic, antioxidant activities and intestinal glucose uptake evaluation of Endiandra kingiana extracts (2020) Biocatal. Agric. Biotechnol., 25; Fukumoto, L.R., Mazza, G., Assessing antioxidant and prooxidant activities of phenolic compounds (2000) J. Agric. Food Chem, 48, pp. 3597-3604; Benzie, I.F.F., Strain, J.J., Ferric reducing/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration (1999) Methods Enzymol, 299, pp. 15-27; Mosmann, T., Rapid colorimetric assay for cellular growth and survival : Application to proliferation and cytotoxicity assays (1983) J. Immunol. Methods., 65, pp. 55-63; Babu, D., Gurumurthy, P., Borra, S.K., Cherian, K.M., Antioxidant and free radical scavenging activity of triphala determined by using different in vitro models (2013) J. Med. Plant Res., 7, pp. 2898-2905; Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E., UCSF Chimera – A Visualization System for Exploratory Research and Analysis (2004) J. Comput. Chem., 25, pp. 1605-1612; Wang, J., Wang, W., Kollman, P.A., Case, D.A., Automatic atom type and bond type perception in molecular mechanical calculations (2006) J. Mol. Graph. Model., 25, pp. 247-260; Huang, C.C., Meng, E.C., Morris, J.H., Pettersen, E.F., Ferrin, T.E., Enhancing UCSF Chimera through web services (2014) Nucleic Acids Res, 42, pp. W478-W484; Bachmann, K., (2009), pp. 303-325. , Chapter 12: Drug – Drug Interactions with an Emphasis on Drug Metabolism and Transport, (1st ed.), Elsevier Inc; Kim, K., Rioux, L., Turgeon, S.L., Phytochemistry Alpha-amylase and alpha-glucosidase inhibition is differentially modulated by fucoidan obtained from Fucus vesiculosus and Ascophyllum nodosum (2014) Phytochemistry, 98, pp. 27-33; Coussens, N.P., Sittampalam, G.S., Guha, R., Brimacombe, K., Dahlin, J.L., Devanaryan, V., Foley, T.L., Austin, C.P., Assay guidance manual: Quantitative biology and pharmacology in preclinical drug discovery (2018) Clin. Transl. Sci, 11, pp. 461-470; Ren, L., Qin, X., Cao, X., Wang, L., Bai, F., Bai, G., Shen, Y., Structural insight into substrate specificity of human intestinal maltase-glucoamylase (2011) Protein Cell, 2, pp. 827-836; Maurus, R., Begum, A., Williams, L.K., Fredriksen, J.R., Zhang, R., Withers, S.G., Brayer, G.D., Alternative catalytic anions differentially modulate human alpha-amylase Activity (2008) Biochemistry, 47, pp. 3332-3344
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