A comprehensive review of quinoline scaffolds in antitubercular drug discovery

Abstract

Tuberculosis (TB), a leading infectious disease caused by Mycobacterium tuberculosis, continues to pose a significant global health challenge, particularly with the rising prevalence of multidrug-resistant and extensively drug-resistant strains. The prolonged and complex nature of current treatment regimens often lead to poor patient adherence, further contributing to drug resistance. The quinoline scaffold has been established as a privileged pharmacophore in medicinal chemistry, evidenced by its incorporation in clinically significant drugs such as ciprofloxacin, moxifloxacin, and bedaquiline. This review provides a comprehensive overview of recent advancements (from 2019 to present) in the synthesis and biological evaluation of quinoline-based compounds as potential anti-TB agents. This review article systematically explores a variety of quinoline derivatives, detailing their synthetic methodologies, in vitro antimycobacterial activities, cytotoxicity profiles, and proposed mechanisms of action for the most efficacious compounds. Notably, several derivatives exhibit therapeutic activity that is superior to or comparable with existing first-line anti-TB therapies. The review emphasizes the critical need for ongoing research to optimize these quinoline scaffolds, investigate novel mechanisms of action, and conduct thorough structure–activity relationship (SAR) studies. Such efforts are essential for the development of highly effective and safe anti-TB agents to combat the alarming rise of drug-resistant tuberculosis.