The Emerging Landscape of Tubercular Targets: A Medicinal Chemistry Approach

Antitubercular drug discovery progress in the last decade, especially research on the biological function, target inhibition and diagnosis of tuberculosis (TB) diagnosis has considerably advanced. The application of target-based drug discovery techniques have become a more powerful tool for medicinal chemists in developing new therapeutic strategies, such as its application in the identification/validation of new targets, new leads, and drug candidates with optimized efficacy. This has been further evidenced by the recent approval of delamanid and bedaquiline for the treatment of MDR-TB and XDR-TB, respectively. While a TB drug pipeline has shown great development, high attrition rates must constantly replenish the pipeline with high-quality leads acting through the inhibition of new targets. This review provides a critical analysis of the approaches used to advance hit compounds into viable lead candidates as well as the possible influence of new targets on drug development in the near future. Finally, we concluded with the present challenges that are faced in TB drug development.