A Test Case: Synthesis and Evaluation of 6‐(Pyrazolyl)‐Indole Hybrid Molecules as Potential Anti‐Tuberculosis Agents

Abstract

In this study, we synthesized and characterized various 6‐(pyrazolyl)‐indole derivatives and characterized using spectroscopic techniques. Substituents including electron‐withdrawing (formyl, nitrile, carboxylic acid, ester, amide, nitro) and donating groups (methylene alcohol, chloro) were introduced at the 5th position of the pyrazole ring, yielding pyrazole‐indole compounds (16a‐16r). These compounds were assessed for anti‐tuberculosis screening against H37Rv and Mycobacterium tuberculosis strains. Notably, 16c, 16j, and 16o showed potent activity (Minimum Inhibition concentration< 25 µg/mL) compared to standard drugs such as Rifampicin, Isoniazid, and Pyrazinamide. Molecular understanding was enhanced through density functional theory (DFT) geometry optimization preceding molecular docking, revealing significant interactions between ligand and protein, supporting the antitubercular activity of 16c, 16j, and 16o.