Synthesis and exploration of in-silico and in-vitro α-glucosidase and α-amylase inhibitory activities of N-(3-acetyl-2-methyl-4-phenylquinolin-6-yl)arylamides

Abstract

In a search for α-amylase and α-glucosidase inhibitors to treat type II diabetes, a new series of N-(3-acetyl-2-methyl-4-phenylquinolin-6-yl)arylamides were synthesized from 3-acetyl-2-methyl-4-phenylquinolines. Initially, nitro function of 1-(2-methyl-6-nitro-4-phenylquinolin-3-yl) ethanone was converted into the corresponding amine by grinding it with zinc dust and ammonium chloride (reducing agent) which in turn successfully converted into the N-(3-acetyl-2-methyl-4-phenylquinolin-6-yl) arylamides by treating it with coupling reagents such as EDC, HATU, and DCC. All the synthesized compounds were found to afford excellent yields with HATU, moderate in EDC, and very less in DCC and hence, HATU was considered as a suitable coupling reagent. These analogs are structurally characterized by NMR, NMR-DEPT, and HRMS. All the synthesized compounds were evaluated for in-silico and in-vitro α-glucosidase and α-amylase inhibitory activity using acarbose as standard and all the compounds showed positive results by in-silico and in-vitro α-amylase inhibition assay. Among the tested compounds, compound 5c and 5d in α-glucosidase as well as in α-amylase are found to have least binding energy value. These compounds found to form more stable ligand–receptor complex amongst other compounds. In addition, in experimental part, also the compounds 5c and 5d exhibited 56.90 ± 0.77% and 59.46 ± 0.61% of the higher potent α-glucosidase inhibitory activity with IC50 values 171.75 ± 3.95 µmol/mL and 171.67 ± 1.57 µmol/mL significantly (p < 0.05) compared to the remaining seven test samples. And similarly, the compound 5c and 5d possessed α-amylase inhibitory activity at a concentration of 100 µg/mL (55.42 ± 0.42% and 55.42 ± 1.14%) with IC50 values 138.92 ± 4.44 µmol/mL and 158.78 ± 2.34 µmol/mL.