Structure‐Based Design and Biological Evaluation of Imidazo[1,2‐ a ]pyridine Derivatives as Potential Antituberculosis Agents

ABSTRACT

A library of 11 novel imidazopyridine‐based sulfonamide derivatives ( 4a–4k ) were synthesized through the coupling of an imidazo[1,2‐ a ]pyridine hydrochloride intermediate with various substituted sulfonyl chloride derivatives ( 3a–3k ). The structures of the compounds ( 4a–4k ) were confirmed using appropriate spectroscopic techniques. The synthesized derivatives ( 4a–4k ) were subsequently evaluated for their antitubercular and antioxidant potential. Among the tested molecules, compounds 4b , 4d , and 4g demonstrated moderate antimycobacterial activity, displaying minimum inhibitory concentration (MIC) values of 6.21 ± 0.45 µg/mL, which were comparable to that of the standard drug rifampicin. To gain insight into their possible mechanism of action, molecular docking studies were carried out against selected tuberculosis (TB)‐associated protein targets. The active compounds exhibited favorable binding interactions within the target binding pockets, supporting the observed biological activity. Furthermore, in silico ADMET assessment revealed encouraging pharmacokinetic characteristics, including good gastrointestinal absorption, satisfactory bioavailability, and compliance with common drug‐likeness criteria without significant rule violations. Collectively, these findings identify the imidazopyridine sulfonamide derivatives as potential lead structures for further structural optimization and biological investigation toward the development of new antitubercular agents.