Anti-tuberculosis lead molecules from natural products targeting Mycobacterium tuberculosis ClpC1

J Ind Microbiol Biotechnol. 2016 Mar;43(2-3):205-12. doi: 10.1007/s10295-015-1709-3. Epub 2015 Nov 19.

Abstract

Tuberculosis (TB) is a serious and potentially fatal disease caused by Mycobacterium tuberculosis (M. tb). The occurrence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tb is a significant public health concern because most of the anti-TB drugs that have been in use for over 40 years are no longer effective for the treatment of these infections. Recently, new anti-TB lead compounds such as cyclomarin A, lassomycin, and ecumicin, which are cyclic peptides from actinomycetes, have shown potent anti-TB activity against MDR and XDR M. tb as well as drug-susceptible M. tb in vitro. The target molecule of these antibiotics is ClpC1, a protein that is essential for the growth of M. tb. In this review, we introduce the three anti-TB lead compounds as potential anti-TB therapeutic agents targeting ClpC1 and compare them with the existing anti-TB drugs approved by the US Food and Drug Administration.

Keywords: Actinomycete; Anti-tuberculosis drugs; ClpC1; Tuberculosis.

Publication types

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

MeSH terms

  • Antitubercular Agents / isolation & purification*
  • Antitubercular Agents / pharmacology*
  • Biological Products / chemistry*
  • Drug Approval
  • Extensively Drug-Resistant Tuberculosis / drug therapy
  • Extensively Drug-Resistant Tuberculosis / microbiology
  • Humans
  • Mycobacterium tuberculosis / classification
  • Mycobacterium tuberculosis / drug effects*
  • Peptides, Cyclic / isolation & purification
  • Peptides, Cyclic / pharmacology
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / microbiology*
  • United States
  • United States Food and Drug Administration

Substances

  • Antitubercular Agents
  • Biological Products
  • Peptides, Cyclic