Cell wall: A versatile fountain of drug targets in Mycobacterium tuberculosis

Biomed Pharmacother. 2017 Nov:95:1520-1534. doi: 10.1016/j.biopha.2017.09.036. Epub 2017 Sep 21.

Abstract

Tuberculosis is the leading infectious disease responsible for an estimated one and a half million human deaths each year around the globe. HIV-TB coinfection and rapid increase in the emergence of drug resistant forms of TB is a dangerous scenario. This underlines the urgent need for new drugs with novel mechanism of action. A plethora of literature exist that highlight the importance of enzymes involved in the biosynthesis of mycobacterial cell wall responsible for its survival, growth, permeability, virulence and resistance to antibiotics. Therefore, assembly of cell wall components is an attractive target for the development of chemotherapeutics against Mycobacterium tuberculosis. The aim of this review is to highlight novel sets of enzyme inhibitors that disrupt its cell wall biosynthetic pathway. These include the currently approved first and second line drugs, candidates in clinical trials and current structure activity guided endeavors of scientific community to identify new potent inhibitors with least cytotoxicity and better efficacy against emergence of drug resistance till date.

Keywords: Cell wall inhibitors; Drug resistance; Drug targets; Mycobacterium cell wall; Mycobacterium tuberculosis; Tuberculosis drug discovery.

Publication types

  • Review

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology*
  • Cell Wall / drug effects*
  • Drug Delivery Systems
  • Humans
  • Mycobacterium tuberculosis / cytology*
  • Mycobacterium tuberculosis / drug effects*
  • Mycolic Acids / chemistry
  • Tuberculosis / drug therapy

Substances

  • Antitubercular Agents
  • Mycolic Acids