Synthesis and evaluation of heterocycle structures as potential inhibitors of Mycobacterium tuberculosis UGM

Bioorg Med Chem. 2020 Jul 1;28(13):115579. doi: 10.1016/j.bmc.2020.115579. Epub 2020 Jun 2.

Abstract

In this study, we screen three heterocyclic structures as potential inhibitors of UDP-galactopyranose mutase (UGM), an enzyme involved in the biosynthesis of the cell wall of Mycobacterium tuberculosis. In order to understand the binding mode, docking simulations are performed on the best inhibitors. Their activity on Mycobacterium tuberculosis is also evaluated. This study made it possible to highlight an "oxazepino-indole" structure as a new inhibitor of UGM and of M. tuberculosis growth in vitro.

Keywords: Docking; Heterocycles; Inhibitor; Mycobacterium tuberculosis; UDP-galactopyranose mutase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / pharmacology
  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / pharmacology
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Intramolecular Transferases / antagonists & inhibitors*
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology
  • Protein Binding
  • Tuberculosis / drug therapy*

Substances

  • Antitubercular Agents
  • Enzyme Inhibitors
  • Indoles
  • butenolide
  • Intramolecular Transferases
  • UDP-galactopyranose mutase
  • 4-Butyrolactone