Mycobacterium tuberculosis Shikimate Pathway Enzymes as Targets for the Rational Design of Anti-Tuberculosis Drugs

Molecules. 2020 Mar 11;25(6):1259. doi: 10.3390/molecules25061259.

Abstract

Roughly a third of the world's population is estimated to have latent Mycobacterium tuberculosis infection, being at risk of developing active tuberculosis (TB) during their lifetime. Given the inefficacy of prophylactic measures and the increase of drug-resistant M. tuberculosis strains, there is a clear and urgent need for the development of new and more efficient chemotherapeutic agents, with selective toxicity, to be implemented on patient treatment. The component enzymes of the shikimate pathway, which is essential in mycobacteria and absent in humans, stand as attractive and potential targets for the development of new drugs to treat TB. This review gives an update on published work on the enzymes of the shikimate pathway and some insight on what can be potentially explored towards selective drug development.

Keywords: Mycobacterium tuberculosis; enzyme drug target; enzyme inhibition; human tuberculosis; rational drug design; shikimate pathway.

Publication types

  • Review

MeSH terms

  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Bacterial*
  • Humans
  • Latent Tuberculosis / drug therapy
  • Latent Tuberculosis / microbiology
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / genetics
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / growth & development
  • Shikimic Acid / antagonists & inhibitors*
  • Shikimic Acid / chemistry
  • Shikimic Acid / metabolism
  • Structure-Activity Relationship
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Shikimic Acid