DFT analysis and in vitro studies of isoxazole derivatives as potent antioxidant and antibacterial agents synthesized via one-pot methodology

Abstract

Isoxazole and its derivatives derived from natural resources are very few. However, they have several applications in pharmaceutical industries, including antimicrobial, antitumor, anticancer, antifungal, and antibacterial activities. As a result, this research aimed to design a novel one-pot green approach to synthesize new oxazole derivatives. The derivatives were further explored for their antibacterial and antioxidant activities together with their density functional theory (DFT) analysis. Characterization of newly synthesized moieties was done by IR, 1H NMR, 13C NMR, CHN analysis, & single-crystal X-ray Crystallography. Further, these compounds were examined for their antibacterial potential by using Gentamycin as a standard drug against S. aureus and E. coli bacterial strains. The derivatives 4a, 4c, 4d, 4f, 4j, and 4k possessed excellent antibacterial potential against former, while 4c and 5 showed the highest activity against the later one. The derivatives were also analyzed for their antioxidant activities by using free radical scavenging (ABTS. & DPPH assays), and total antioxidant capacity. Here also, 4a, 4d, 4e, 4k, 4l, 4m, and 5 exhibited the most promising results. Finally, the DFT analysis was achieved by using the B3LYP methodology with a 6–311 + G(d,p) basis set to study the electronic structure of molecules and analysis of chemical reactivity descriptors such as hardness (η), Mulliken electronegativity (χ), chemical potential (μ) and electrophilicity (ω). These properties were calculated from the levels of the predicted frontier molecular orbitals and their energy gap.