Recent advancements and developments in search of anti-tuberculosis agents: A quinquennial update and future directions

Tuberculosis (TB) has been considered as the highly chronic, contagious and infectious disorder caused by Mycobacterium tuberculosis (Mtb). Every year more than 10 million patients found ill with TB and 1.5 million of them die due to TB. Currently used directly observed treatment short course has completely failed due to emergence of resistance such as multi-drug resistant tuberculosis (MDR-TB), extensively drug resistant tuberculosis (XDR-TB) and total drug-resistant tuberculosis (TDR-TB). In last forty-six years, only a few drugs namely bedaquiline, delamanid, and pretomanid have been approved for treatment of MDR-TB. In search of the panacea for tuberculosis, several anti-mycobacterial agents have been designed, synthesized and evaluated for anti-tuberculotic activity by several research groups and organizations. Recently, the research endeavour in search of anti-TB agents have extensively studied due to in silico techniques such as molecular docking, 3-dimensional quantitative structure activity relationships (3D-QSAR); dynamic simulations; target driven anti-TB drug discovery approach; phenotypic screening and pharmacokinetic-toxicity determination through in silico and or in vivo models. Further, the recent trend has been shifted to adopt the design and synthesis of novel scaffold or entirely new chemical classes acting on the new targets may result in possibly less instances of resistance development. The present review shall provide not only the complete coverage of newly identified anti-TB agents but also impart spontaneous intuition to reader of this journal to choose the suitable scaffolds of interest in search of anti-TB potential.