Synthesis, Characterization, Antitubercular Activity, and Molecular Docking Studies of Pyrazolylpyrazoline-Clubbed Triazole and Tetrazole Hybrids

[Image: see text] To increase the antitubercular potency, we synthesized a series of novel pyrazolylpyrazoline derivatives (9a–p) using the one-pot multicomponent reaction of the substituted heteroaryl aldehyde (3a,b), 2-acetyl pyrrole/thiazole (4a,b), and substituted hydrazine hydrates (5–8) in the presence of base NaOH as a catalyst in ethanol as the solvent at room temperature. Substituted heteroaryl aldehyde (3a,b) was synthesized from 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-methyl-carbaldehyde on protection with ethylene glycol followed by treatment with 4-amino triazole/5-amino tetrazole and then deprotection using acid. The salient features of the green protocol are the one-pot reaction, shorter reaction time, and straightforward workup procedure. All of the compounds were tested against Mycobacterium tuberculosis H(37)Rv, wherein compounds 9i, 9k, 9l, 9o, and 9p were found to be most effective. The structures of newly synthesized compounds were determined using spectral methods. Furthermore, molecular docking investigations into the active site of mycobacterial InhA yielded well-clustered solutions for these compounds’ binding modalities producing a binding affinity in the range from −8.884 to −7.113. Theoretical results were in good accord with the observed experimental values. The docking score of the most active compound 9o was found to be −8.884, and the Glide energy was −61.144 kcal/mol. and it was found to accommodate well into the active site of InhA, engaging in a network of bonded and nonbonded interactions.