Synthesis, characterization and biological activity of some isoxazole derivatives via 1,3-dipolar cycloaddition reaction of nitrile oxide

Background and objective: Isoxazoles are significant heterocyclic products that are used in various applications in the field of medicinal chemistry. Along with prescription drugs, a variety of bioactive pharmaceutical substances, such as valdecoxib, leflunomide, and danazol, include the isoxazole core. The present work aimed to synthesize and test the antibacterial, antioxidant, and antifungal activities combined with the theoretical investigations. Methods: Various 2,4-disubstituted isoxazoles have been synthesized through a 1,3-dipolar cycloaddition reaction via nitrile oxide. The structures of synthesized compounds were fully characterised by multinuclear NMR spectroscopy. Anti-bacterial activity was investigated against Escherichia coli and Staphylococcus aureus by Muller Hinton agar using agar diffusion method. The biological effect of the synthesized compounds was investigated with the docking study. Results: Herein, nine new target compounds were synthesized in moderate to high isolated yield. Naphthalene and chlorophenyl isoxazole substitutes have been found to enclose a higher effectiveness against bacterial, fungus and radical scavenging abilities based on the docking binding site energy.Compounds5a-e exhibited various antibacterial activities against Escherichia coli as gram-negative bacteria ranging from 21 to 40 mm of the inhibitory zone (30 µg). The compound 5eexhibiteda significant antioxidant activity using the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (97.8 %). A range of docking energy scores between -9.4 and -13.7Kcal/mol were observed for the compounds5a-g and 9a-c. Conclusion: The newly synthesized 2,4-disubstituted isoxazole compounds could serve as potent leads for the development of antimicrobial agents. Keywords: Antibacterial; Antioxidant,; 1,3-Dipolar Cycloaddition; Insilico; Isoxazole derivatives