Exploring Indole-Linked Triazole Sulfonamide Derivatives as Potent Mycobacterial Carbonic Anhydrase Inhibitors: Leveraging a Tail Approach for the Design, Synthesis, andStudies─An In-Depth Multidisciplinary Study.

The alarming rise of multidrug-resistant tuberculosis (MDR-TB) underscores the urgent need for new classes of antitubercular agents targeting novel pathways. To address this, a series of indole triazole sulfonamides were rationally designed, incorporating an indole pharmacophore hybridized with a triazole linker containing a sulfonamide group. Compoundhad the highest anti-TB efficacy againstwith a MIC of 0.25 μg/mL. Additionally, compoundsandelicited activity of 2 μg/mL. All potent compounds exhibited better safety profiles and selectivity. Compoundsandare additive, whileis synergistic with rifampicin. Compoundhad promising activity against drug-resistant strains of, highlighting its potential to address MDR-TB. The compounds were evaluated for MtCA inhibitory activity. The- and-substituted derivatives demonstrated varying degrees of inhibition, with stronger inhibition observed for MtCA2. The potential of compoundas a promising antitubercular agent was further strengthened byligand-target interaction.