Lipolytic enzymes inhibitors: A new way for antibacterial drugs discovery

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains the deadliest infectious disease worldwide with 1.5 million deaths in 2018, of which about 15% are attributed to resistant strains. Another significant example is abscessus abscessus), a nontuberculous mycobacteria (NTM) responsible for cutaneous and pulmonary infections, representing up 95% NTM infections cystic fibrosis (CF) patients. M. new clinically relevant pathogen considered one most drug-resistant standardized chemotherapeutic regimens lacking. Together emergence tb multi-drug strains ineffective expensive therapeutics, have paved way development classes anti-mycobacterial agents offering additional therapeutic options. In this context, specific inhibitors mycobacterial lipolytic enzymes represent novel promising antibacterial molecules address challenging issue. The results highlighted here include complete overview activities, either broth medium or inside infected macrophages, two families potent multi-target agents, i.e. oxadiazolone-core compounds (OX) Cyclophostin & Cyclipostins analogs (CyC); identification biochemical validation their effective targets (e.g., antigen 85 complex TesA playing key roles mycolic acid metabolism) together respective crystal structures. To our knowledge, these first able target impair replicating as well intracellular bacteria. We impelled deciphering mode action finding potential against mycobacterial-related diseases.