Design, synthesis, alpha-amylase inhibition and in silico docking study of novel quinoline bearing proline derivatives

摘要

alpha-amylase enzyme hydrolyses carbohydrate into glucose is known to be an important molecular target for type 2 Diabetes mellitus. In the course of developing alpha-amylase enzyme inhibitors, we designed, synthesized seventeen novel quinoline bearing proline analogs, subsequently physico-chemical properties of designed analogs were also in silico predicted for their drug likeness evaluation. Synthesized compounds were characterized by spectral analysis such as Mass, IR, H-1 NMR, C-13 NMR and further screened in vitro for alpha-amylase inhibitory activity using acarbose as standard drug. Seven analogs, 6a, 6b, 6c, 6d, 6g, 10b and 10c showed significant alpha-amylase inhibitory activity. Eight analogs, 5, 6e, 6f, 6h, 6j, 10a, 10d and 10e showed good to moderate activity while other two analogs, 6i and 9 showed least activity. The molecular docking study of significantly active and weakly active compounds was performed in order to study their putative binding mode of the most and least active compounds (6c and 6i). (C) 2020 Elsevier B.V. All rights reserved.