Mycobacterial Membrane Protein Large 3 (MmpL3) Inhibitors: A Promising Approach to Combat Tuberculosis

ChemMedChem. 2021 Oct 15;16(20):3136-3148. doi: 10.1002/cmdc.202100359. Epub 2021 Aug 3.

Abstract

Tuberculosis is a prominent aliment throughout the world and a leading cause of mortality among infectious diseases. Drug development for multi-drug resistance and reducing the current therapy time is the top priority. Mycobacterial membrane protein large 3 (MmpL3) is a promising target with high potential, however, it has not been explored to its greatest potential. It is a membrane transporter that translocates trehalose-monomycolate which is a precursor for the synthesis of mycolic acid that is essential for the synthesis of the bacterial cell wall and is pathogenic in nature. In this review, we have discussed the current development of MmpL3 inhibitors, different scaffolds, their derivatives, and their synthetic schemes and provide insight into the challenges in developing these inhibitors.

Keywords: MmpL3; antibiotics; antimycobacterial; cell wall biosynthesis; inhibitors; mycolic acid; trehalose-monomycolates; tuberculosis.

Publication types

  • Review

MeSH terms

  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Humans
  • Membrane Transport Proteins / metabolism
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Tuberculosis / drug therapy*
  • Tuberculosis / metabolism

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Membrane Transport Proteins
  • MmpL3 protein, Mycobacterium tuberculosis