Design, synthesis, in vitro and in silico studies of 2, 3-diaryl benzofuran derivatives as antitubercular agents

Bioorg Chem. 2020 Jun:99:103784. doi: 10.1016/j.bioorg.2020.103784. Epub 2020 Apr 7.

Abstract

As a part of our drug discovery program for anti-tubercular agents, a total of seventeen 2, 3-diaryl benzofuran hybrids were designed, synthesized and screened for their anti-tubercular potential against Mycobacterium tuberculosis H37Ra avirulent strain. Out of seventeen, four derivatives showed significant activity against M. tuberculosis H37Ra avirulent strain (ATCC 25177) with MIC value ranging from 12.5 to 50 µg/mL but out of four, one derivative (9E) was significantly active (MIC 12.5 μg/mL), which was further supported by the molecular docking energy (-8.4 kcal/mol) with respect to the first line anti-tubercular drug, isoniazid (-6.2 kcal/mol) on the target Polyketide Synthase-13. All the derivatives were also evaluated for their cytotoxicity against the normal lung cell line L-132 by the MTT assay and no toxicity was observed up to 27.4 µg/mL concentration. This report on the antitubercular potential of benzofuran derivatives may be of great help in anti-tubercular drug development.

Keywords: Anti-tubercular activity; Benzofuran; In-silico studies; Semi-synthetic derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry
  • Benzofurans / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Structure-Activity Relationship

Substances

  • Antitubercular Agents
  • Benzofurans
  • benzofuran