Potent Broad‐Spectrum Antimicrobials Based on Indene‐Fused Thiazolidinone and Thiazolopyrimidine Scaffolds: Design, Synthesis, and Molecular Insights

The rise of antimicrobial resistance highlights the urgent need for new therapeutic scaffolds. In this work, indene‐fused heterocycles bearing thiazolidinone and thiazolopyrimidine frameworks were synthesized from 2‐indanone and characterized by spectroscopic methods. The compounds were evaluated against Staphylococcus aureus , Escherichia coli , and Candida albicans . Among them, compounds 5 and 14 displayed potent broad‐spectrum activity (MIC = 3.125 μg/mL), equaling chloramphenicol against S. aureus and outperforming cephalothin against E. coli . Structure–activity relationship analysis revealed that electron‐withdrawing substituents and fused heterocycles markedly enhanced potency. Molecular docking confirmed strong binding of compounds 5 and 14 to bacterial DNA gyrase B (1HSK), surpassing reference antibiotics. These findings demonstrate the potential of indene‐based scaffolds as promising candidates for antimicrobial drug development.