Green synthesis of 3-methyl-4-(hetero)aryl methylene isoxazole-5(4H)-ones using WEOFPA/glycerol: evaluation of anticancer and electrochemical behaviour properties

Abstract

In the present study, the MCRs of hydroxylamine hydrochloride and ethyl acetoacetate with various substituted aromatic and heteroaromatic aldehydes reacted to produce 3-methyl-4-(hetero)aryl methylene isoxazole-5(4H)-ones derivatives catalyzed by an agro-waste-based solvent medium in an oil bath at 60 °C with stirring. The developed protocol features several advantages, such as being benign and eco-friendly, efficient, avoiding the use of hazardous solvents, and inexpensive, while giving isoxazole derivatives in an 86–92% yield. The homogeneity of the product was confirmed by various spectroscopic analyses. Further, in vitro anticancer evaluation of the synthesized compounds (4h–4o) against lung cancer cells was performed, and among them, 4j, 4k, 4m, and 4o exhibited excellent anticancer activity and compounds 4i and 4n moderate inhibitory activity against lung cancer A549 cells to the reference drug doxorubicin. Furthermore, the derivatives were subjected to electrochemical behaviour studies using cyclic voltammetry and they showed intensive oxidation and reduction potential and also showed excellent anti-oxidant agents. Based on this research study, more and more novel structures of isoxazoles are being designed and synthesized, and their electrochemical behaviour and anticancer activities are studied for the development of novel drug-like candidates.