Abstract

SYNTHESIS AND ANTIMICROBIAL EVALUATION OF NEW ISOXAZOLE ANALOGUES & THEIR DERIVATIVES

Ravinder Kumar*, Jonny Kumar and Yash Pratap Singh Rana

ABSTRACT

The present study reports the design, synthesis, structural characterization, and antimicrobial evaluation of novel isoxazole derivatives containing electron-withdrawing and electron-donating substituents on aromatic rings. Isoxazole, a five-membered heterocycle bearing adjacent nitrogen and oxygen atoms, has garnered attention due to its wide spectrum of biological activities, including antibacterial, antifungal, antiviral, anti-inflammatory, and antineoplastic properties.A series of compounds—V-1 to V-4—were synthesized via a two-step synthetic approach involving the condensation of substituted acetophenones with 2-nitrobenzaldehyde, followed by cyclization with sodium acetate and NaOH under reflux in ethanol. The resulting derivatives were:• V-1: 3-(4-Chloro-phenyl)-5-[2-(2-nitro-phenyl)-vinyl]-isoxazole• V-2: 3-(4-Fluoro-phenyl)-5-[2-(2-nitro-phenyl)-vinyl]-isoxazole• V-3: 3-(4-Methoxy-phenyl)-5-[2-(2-nitro-phenyl)-vinyl]-isoxazole• V-4: 3-(4-Bromo-phenyl)-5-[2-(2-nitro-phenyl)-vinyl]-isoxazoleCharacterization was carried out through FTIR, ¹H-NMR, mass spectrometry, and elemental analysis, with melting point and Rf values confirming compound purity. All derivatives exhibited characteristic IR bands (C=C, Ar-NO₂, Ar–X), and NMR data indicated the successful formation of isoxazole rings with expected proton shifts. The synthesized compounds were screened for in vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Micrococcus luteus, Penicillium chrysogenum, and Aspergillus niger. Notably, compounds V-1 and V-2 demonstrated significant antimicrobial potency, particularly against P. aeruginosa and Enterococcus faecalis at concentrations of 25–125 µg/ml. All compounds were active against both Gram-positive and Gram-negative strains, highlighting their broad-spectrum potential. This study underlines the utility of substituted isoxazoles as promising scaffolds for the development of future antimicrobial agents.

Keywords: Anticonvulsant activity, Antitumor activity, Anti-inflammatory, Antimicrobial activity, Antitumor, Enzyme inhibiter activity, Isoxazole derivatives, Heterocyclic compounds, FTIR, ¹H-NMR, Antibacterial activity, Substituted acetophenones, Pseudomonas aerug