Synthesis, biological evaluation of ortho-carboxamidostilbenes as potential inhibitors of hyperglycemic enzymes, and molecular docking study
Document Type
Article
Publication Date
12-5-2021
Abstract
A new series of ortho-carboxamidostilbenes derivatives were synthesized via Heck Coupling and screened for their alpha-amylase and alpha-glucosidase inhibitory potential. The results indicated that all the synthesized compounds showed a substantial alpha-glucosidase inhibitory potential (IC50 between 3-78 mu g/mL) compared to acarbose (IC50 = 16.14 +/- 1.05 mu g/mL) as the standard. In addition, the IC50 values against alpha-amylase varying from 3-300 mu g/mL when compared to a standard drug acarbose (IC50 = 21.12 +/- 0.29 mu g/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 (alpha-glucosidase) and alpha-amylase, respectively. The interaction modes of 5d (IC50 = 2.90 +/- 0.58 mu g/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 mu g/mL) in alpha-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. (C) 2021 Elsevier B.V. All rights reserved.
Keywords
Ortho-carboxamidostilbenes, Heck coupling, Alpha-amylase, Alpha-glucosidase, Molecular docking
Divisions
Science
Funders
Universiti Sains Malaysia[1001.PKIMIA.8012310],MyPair PHC Hibiscus[203.PKIMIA. 6782002]
Publication Title
Journal of Molecular Structure
Volume
1245
Publisher
Elsevier
Publisher Location
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS