Synthesis, Biological Evaluation of ortho-Carboxamidostilbenes as Potential Inhibitors of Hyperglycemic Enzymes, and Molecular Docking Study

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


Abstract

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

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

doi: 10.1016/j.molstruc.2021.131007

Issn: 00222860

Type:


References

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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