Design, synthesis, in vitro, and in silico anti-α-glucosidase assays of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives as new anti-diabetic agents
Mohammad Hosein Sayahi, Samira Zareei, Mohammad Halimi, Majid Alikhani‐Koupaei, Ali Moazzam, Maryam Mohammadi‐Khanaposhtani, Somayeh Mojtabavi, Mohammad Ali Faramarzi, Hossein Rastegar, Parham Taslımı, Essam H. Ibrahim, Hamed A. Ghramh, Bagher Larijani, Mohammad Mahdavi
Abstract
In this work, a novel series of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives 5a-n were designed by consideration of the potent α-glucosidase inhibitors containing indole and carboxamide-1,2,3-triazole-N-phenylacetamide moieties. These compounds were synthesized by click reaction and evaluated against yeast α-glucosidase. All the newly title compounds demonstrated superior potency when compared with acarbose as a standard inhibitor. Particularly, compound 5k possessed the best inhibitory activity against α-glucosidase with around a 28-fold improvement in the inhibition effect in comparison standard inhibitor. This compound showed a competitive type of inhibition in the kinetics. The molecular docking and dynamics demonstrated that compound 5k with a favorable binding energy well occupied the active site of α-glucosidase.