Design and synthesis of 4-Aminoquinoline-isoindoline-dione-isoniazid triads as potential anti-mycobacterials

Bioorg Med Chem Lett. 2020 Nov 15;30(22):127576. doi: 10.1016/j.bmcl.2020.127576. Epub 2020 Sep 24.

Abstract

A series of 4-aminoquinoline-isoindoline-dione-isoniazid triads were synthesized and assessed for their anti-mycobacterial activities and cytotoxicity. Most of the synthesized compounds exhibited promising activities against the mc26230 strain of M. tuberculosis with MIC in the range of 5.1-11.9 µM and were non-cytotoxic against Vero cells. The conjugates lacking either isoniazid or quinoline core in their structural framework failed to inhibit the growth of M. tuberculosis; thus, further strengthening the proposed design of triads in the present study.

Keywords: 4-aminoquinoline-isoindoline-dione-isoniazid; Anti-mycobacterial activity; Cytotoxicity; Molecular docking; Selectivity index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Isoniazid / chemistry
  • Isoniazid / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Structure-Activity Relationship

Substances

  • Aminoquinolines
  • Antitubercular Agents
  • Indoles
  • indoline
  • 4-aminoquinoline
  • Isoniazid