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

•A new series of ortho-carboxamidostilbenes were synthesized and characterized.•Compound 5a-5e were evaluated for in vitro α-amylase and α-glucosidase inhibitory activity.•Compound 5e was found potent α-amylase inhibitor and compound 5d was found potent α-glucosidase inhibitor.•Kinetic studies suggested compound 5e represented a combination of competitive and uncompetitive inhibition on α-amylase, while compound 5d displayed a non-competitive inhibition on α-glucosidase enzyme.•In silico studies were carried out to understand the binding interaction between active compounds and enzymes 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.