Facile Ring Opening of Novel Bisoxazolone with Substituted Aromatic Amines: Synthesis, Antimicrobial, Antioxidant Potential, In Silico ADME Profile and Molecular Docking Study

This article describes the controlled synthesis and characterization of an olefin-linked oxazolone scaffold compound containing multifunctional groups, including the carbonyl group, imine, and carbon-carbon double bond. The reaction of the bisoxazolone with aromatic amines led to the ring-opening of the bisoxazolone into the corresponding bisdiamide derivatives in a short time (average 10 min), resulting in a high yield (>90 %). The compounds were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and MS. Besides, screened against Escherichia coli, Staphylococcus aureus, and Candida albicans using ciprofloxacin as a standard. All compounds exhibited significant inhibition potency against E. coli, with a lower potency against S. aureus. Compounds 3 a, 3 b, and 3 d showed more reactivity against E. coli, while compound 3 i has the highest activity against S. aureus (MIC=128 μg/mL). Additionally, the antioxidant activity was performed utilizing DPPH radical scavenging activity. The findings indicated that some compounds possessed moderate antioxidant activity in comparison to ascorbic acid as a control. A molecular docking study demonstrated a positive interaction between synthesized compounds and the bacterial DNA gyrase target (PDB ID: 1KZN) in S. aureus. Subsequently, in silico ADME simulations were conducted for all the synthesized compounds, indicating favorable properties in comparison to the established antibiotic ciprofloxacin.