Quinolin(on)es and pyridin(on)es as promising scaffolds against mycobacterial infections

Mycobacterial infections pose a significant global health challenge. In 2024, 1.23 million deaths were associated with M. tuberculosis (M.tb). In recent years, the number of recorded cases of non-tuberculous mycobacterial infections has risen, particularly among elderly patients or people with underlying pulmonary diseases. Due to the emergence of antibioresistance, the discovery of new drugs which target essential enzymes in mycobacteria is required to move towards new therapeutic options for future years. Some current clinical drugs contain promising scaffolds, which serve as a basis for other researches in medicinal chemistry. The increasing interest of quinoline, quinolone, pyridine and pyridone cores is driven by their promising biological effects, initially as antibacterial agents, and more specifically, as antimycobacterial agents. The drug discovery strategy focuses on three main biological targets: the mycolic acids biosynthesis, the mycobacterial energy metabolism and DNA metabolism. Hence, this review aims to highlight the development of novel antimycobacterial agents, based on these four promising scaffolds by presenting the design strategy and biological results of recent studies.