Isoniazid-phytochemical conjugation: A new approach for potent and less toxic anti-TB drug development

Chem Biol Drug Des. 2020 Aug;96(2):714-730. doi: 10.1111/cbdd.13685. Epub 2020 May 14.

Abstract

Mycobacterium tuberculosis (Mtb) causes one of the most grievous pandemic infectious diseases, tuberculosis (TB), with long-term morbidity and high mortality. The emergence of drug-resistant Mtb strains, and the co-infection with human immunodeficiency virus, challenges the current WHO-TB stewardship programs. The first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF), have become extensively obsolete in TB control from chromosomal mutations during the last decades. However, based on clinical trial statistics, the production of well-tolerated anti-TB drug(s) is miserably low. Alternately, semi-synthesis or structural modifications of first-line obsolete antitubercular drugs remain as the versatile approach for getting some potential medicines. The use of any suitable phytochemicals with INH in a hybrid formulation could be an ideal approach for the development of potent anti-TB drug(s). The primary objective of this review was to highlight and analyze available INH-phytochemical hybrid research works. The utilization of phytochemicals through chemical conjugation is a new trend toward the development of safer/non-toxic anti-TB drugs.

Keywords: Mycobacterium tuberculosis; INH-phytochemical hybrid; co-infection with human immunodeficiency virus; first-line anti-TB drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology
  • Benzaldehydes / chemistry
  • Drug Development
  • Glycosides / chemistry
  • Humans
  • Indoles / chemistry
  • Isoniazid / adverse effects
  • Isoniazid / chemistry*
  • Isoniazid / pharmacology
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Naphthoquinones / chemistry
  • Phytochemicals / adverse effects
  • Phytochemicals / chemistry*
  • Phytochemicals / pharmacology
  • Steroids / chemistry
  • Structure-Activity Relationship
  • Terpenes / chemistry
  • Tuberculosis / drug therapy*
  • Tuberculosis, Multidrug-Resistant

Substances

  • Antitubercular Agents
  • Benzaldehydes
  • Glycosides
  • Indoles
  • Naphthoquinones
  • Phytochemicals
  • Steroids
  • Terpenes
  • indole
  • vanillin
  • Isoniazid