Design, Synthesis, Antimicrobial Evaluation and Molecular Docking Study of Novel Fused Pyrazole‐Based Heterocycles Featuring Nitrogen and Sulfur Heteroatoms

A new series of fused pyrazole‐based heterocycles was synthesized from 3‐pyridyl hydrazine and benzylidene malononitrile via cyclization with diverse nucleophiles. The resulting pyrazolo[3,4‐d]pyrimidines, thiazoles, thiazines, and thiazolidinones were characterized by IR, 1 H‐NMR, and elemental analysis. Several derivatives displayed potent antimicrobial activity, notably thiazolidinone (12) , dithione (9) , and diphenyl‐pyrazolopyrimidine‐thione (19b) , with MICs as low as 3.125 μg/mL, comparable to standard drugs. Structure–activity analysis revealed that fused frameworks and sulfur‐containing groups enhanced bioactivity. Molecular docking against the bacterial ribosomal protein (PDB ID: 3g7b) confirmed strong binding, with compound 19b showing the best interaction (Δ G = −5.75 kcal/mol). These findings highlight fused pyrazole–sulfur scaffolds as promising candidates for antimicrobial drug development.