A Test Case for the Synthesis of a Hybrid 6‐(pyrazolyl)‐indole Molecules: Anti‐tuberculosis Evaluations and In‐silico Studies

Abstract In this study, we synthesized and characterized various 6‐(pyrazolyl)‐indole derivatives using various spectroscopic techniques ( 1 H, 13 C, FT‐IR and Mass). 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 ( 16 a – 16 r ). These compounds were assessed for anti‐tuberculosis screening against H37Rv and Mycobacterium tuberculosis strains. Notably, 16 c , 16 j , and 16 o showed potent activity (Minimum Inhibitory Concentration <25 μg/mL) compared to standard drugs such as Rifampicin, Isoniazid, and Pyrazinamide. Molecular level 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 16 c , 16 j , and 16 o .