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

Abstract

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.