Quinolidene based monocarbonyl curcumin analogues as promising antimycobacterial agents: Synthesis and molecular docking study

Bioorg Med Chem Lett. 2017 Feb 15;27(4):922-928. doi: 10.1016/j.bmcl.2017.01.004. Epub 2017 Jan 5.

Abstract

A series of quinoline incorporated monocarbonyl curcumin analogues was efficiently synthesized using [HDBU][HSO4] as catalyst via Knoevenagel type condensation and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG in dormant state. The analogues 3e, 3h, 4a and 4e exhibited very good antitubercular activity. The antiproliferative activity of the analogues against MCF-7, A549 and HCT-116 cell lines was evaluated using modified MTT assay and these compounds were found to be non-cytotoxic. Molecular docking study has been carried out against M. tuberculosis pantothenate synthetase (MTB PS) enzyme in an effort to enhance the understanding of their action as antitubercular agents. The potency, low cytotoxicity and selectivity of these analogues support them as valid leads for further optimization.

Keywords: Antitubercular activity; Cytotoxicity; Green protocol; Knoevenagel condensation; Molecular docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Cell Line, Tumor
  • Curcumin / analogs & derivatives*
  • Curcumin / chemical synthesis
  • Curcumin / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Mycobacterium bovis / drug effects
  • Mycobacterium tuberculosis / drug effects
  • Quinolines / chemistry*

Substances

  • Antitubercular Agents
  • Quinolines
  • Curcumin