Design, Synthesis, Spectral Characterization, and Antimicrobial Evaluation of Novel Indole‐2‐Carbohydrazide Derivatives: Experimental and Computational Insight

ABSTRACT The investigation for efficient and nontoxic antimicrobial medication is an imperative subject in drug design and discovery. In this study, we report the synthesis, spectral characterization, and antimicrobial evaluation of novel 3,5‐disubstituted‐ N ′‐((2‐hydroxynaphthalen‐1‐yl)methylene)‐1 H ‐indole‐2‐carbohydrazides 3(a–f) and their derivatives 4(a–f) and 5(a–f) . The structure of these compounds was confirmed by IR, 1 H and 13 C NMR, mass spectrometry, and elemental analysis. In the present study, the Becke, three‐parameter, Lee–Yang–Parr (B3LYP) functional was employed to explore the electronic structure and behavior of the investigated compounds. The synthesized compounds were evaluated in vitro for antimicrobial activity against Staphylococcus aureus , Escherichia coli , Salmonella Typhi , Candida albicans , Aspergillus flavus , Aspergillus niger , and Mycobacterium tuberculosis . Among them, compounds 3a, 3b, 4e, 5a, 5b, 5c, and 5e exhibited excellent antimicrobial activity with minimum inhibitory concentration values 1.56–6.25 µg/mL, comparable to standard drugs. Drug‐likeness predictions and in silico molecular docking and dynamics studies against mycobacterial enoyl reductase (InhA; PDB ID: 4TZK) further supported their potential as promising antimicrobial candidates.