Development of Novel Furan–Chalcone Derivatives as Targeting Bacterial DNA Gyrase and Topoisomerase IV: Design, Synthesis, and In Silico Studies

ABSTRACT A series of novel furan–chalcone derivatives ( Na1–Na8 ) were synthesized and evaluated for their antimicrobial, antioxidant, DNA gyrase inhibitory, and computational properties using integrated in vitro and in silico approaches. Among the synthesized compounds, Na5 exhibited the most potent antibacterial activity with low MIC values against both Gram‐positive and Gram‐negative bacterial strains. Antioxidant studies revealed significant free radical scavenging activity for Na3 , Na4 , and Na5 . Molecular docking studies against DNA gyrase B demonstrated favorable binding interactions within the ATP‐binding pocket. Enzyme inhibition studies against Escherichia coli DNA gyrase and topoisomerase IV confirmed that Na5 showed the strongest inhibitory activity among the tested compounds. ADME predictions indicated acceptable drug‐likeness and pharmacokinetic properties. Furthermore, DFT analysis of Na5 revealed a suitable HOMO–LUMO energy gap and favorable electronic properties supporting its biological activity. Overall, the results identify Na5 as a promising lead candidate for the development of novel antimicrobial agents targeting bacterial DNA gyrase and topoisomerase IV.