Targeting opportunities presented by the pyrimidine biosynthesis pathway in Mycobacterium tuberculosis: a brief review

: Mycobacterium tuberculosis (MTB) is the etiologic agent of tuberculosis (TB) in humans, an infectious disease that continues to be a significant global health concern. The long-term use of multiple anti-tubercular agents may result in patient non-compliance and increased drug toxicity, which could contribute to the emergence of drug-resistant MTB strains that are not susceptible even to second-line available drugs. It is therefore imperative that new antitubercular drugs and vaccines are developed. The peculiar traits of MTB, such as the biochemical and structural features of vital metabolic pathways, can be assessed to identify possible targets for drug development. Enzymes involved in pyrimidine metabolism may be suitable drug targets for TB, given that this pathway is essential for mycobacteria and comprises enzymes that differ from those found in humans. Here, we focused on reviewing the state of the art concerning the therapeutic opportunities presented by the pyrimidine biosynthetic pathway (PBP) as a potential source of enzymes that could be targeted for the treatment of TB. We selected essential enzymes belonging to the PBP for which we identified the existence of a drug discovery pipeline at both the preclinical and clinical levels. Moreover, we emphasize the biochemical and structural characteristics that are pertinent to the development of pharmaceutical agents. These include the molecular details that can ensure selectivity towards the pathogen's proteins.