Nitrofuranyl derivatives as promising antitubercular agents: Structural insights and drug discovery perspectives

The emergence of MDR (multidrug-resistant) and XDR (extensively drug-resistant) variants of Mycobacterium tuberculosis has contributed to the universal resurgence of tuberculosis (TB). Nitrofuran-based compounds, traditionally used as antibacterial agents, have recently gained attention for their potential antitubercular properties. This review presents a comprehensive overview of structural classes of nitrofuran derivatives—including nitrofuranylamides, hydrazides, triazoles, spirocyclic hybrids, and prodrugs—and their corresponding structure–activity relationships, efficacy profiles, and safety evaluations. Several lead compounds exhibit potent in vitro as well as in vivo activity, often surpassing the effectiveness of existing TB drugs while maintaining favorable cytotoxicity and selectivity indices. Repurposing strategies and chemical modifications have significantly improved their pharmacological profiles, offering promising avenues for TB drug discovery. While current findings are encouraging, further mechanistic studies, pharmacokinetic optimization, and translational research are essential to advance nitrofuran derivatives toward clinical application. This review underscores the therapeutic value of nitrofuran scaffolds and supports their continued exploration as viable candidates in the global effort to combat TB. • Multidrug-resistant (MDR/XDR) mycobacterium tuberculosis necessitates novel drug scaffolds. • Nitrofuran derivatives exhibit potent in vitro and in vivo antitubercular activity. • Structural classes include nitrofuranylamides, hydrazides, triazoles, spirocyclic hybrids, and prodrugs. • Structure–activity relationship (SAR) studies highlight key functional group modifications. • Several leads surpass standard TB drugs with favorable safety and selectivity indices. • Repurposing and chemical optimization advance nitrofurans toward clinical translation. • Computational approaches, including SAR and QSAR modeling, accelerate nitrofuran lead optimization. • Nitrofuranyl scaffolds represent promising candidates for next-generation TB drug discovery programs.