Synthesis and study of the α-amylase inhibitory potential of thiadiazole quinoline derivatives

Bioorg Chem. 2017 Oct;74:179-186. doi: 10.1016/j.bioorg.2017.08.003. Epub 2017 Aug 12.

Abstract

α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1-30), characterized by different spectroscopic techniques such as 1HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC50 values ranges between 0.002±0.60 and 42.31±0.17μM which is many folds better than standard acarbose having IC50 value 53.02±0.12μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established.

Keywords: SAR; Synthesis; Thiadiazole quinoline; α-Amylase inhibitory potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Docking Simulation
  • Molecular Structure
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Swine
  • Thiadiazoles / chemical synthesis
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology*
  • alpha-Amylases / antagonists & inhibitors*
  • alpha-Amylases / metabolism

Substances

  • Enzyme Inhibitors
  • Quinolines
  • Thiadiazoles
  • alpha-Amylases