Ionic Liquid-Catalyzed Multicomponent Synthesis of Isoxazole-5(4H)-ones: in vitro Activities and Principal Component Analysis

Heterocycles of the isoxazolone class stand out in the pharmaceutical field because they have numerous biological properties, such as antioxidant, antifungal and antibacterial properties. Thus, isoxazole derivatives have attracted the attention of organic researchers, and several procedures have been developed to obtain these compounds. The present study aimed to synthesize 17 derivatives of isoxazol-5(4H)-ones using a multicomponent reaction catalyzed by an acidic ionic liquid, which allowed yields from 20-96% of the products. To evaluate the bioactivity of the compounds, the synthesized derivatives were analyzed at various concentrations against bacteria and fungi; the derivatives, in general, showed a moderate activity of 125 μg mL^-1 against the fungus Candida tropicalis (ATCC 13803) and four derivatives showed an inhibition of < 15.62 μg mL^-1 for Gram-positive Staphylococcus epidermidis (ATCC 12228). Furthermore, the antioxidant potential of the derivatives was evaluated by measuring their ability to scavenge 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radicals, resulting in a remarkable reduction percentage of up to 81.06%. To gain further insights into the structure-activity relationships, a principal component analysis was conducted to classify the compounds into active and inactive classes, providing a comprehensive understanding of their bioactivity profiles.

Keywords:
isoxazolone derivatives; multicomponent reaction; bioactivity; antioxidant; quantum-chemical descriptors