Synthesis, Computational, Anticancer, and Electrochemical Behavior Studies of 3‐Methyl‐4‐(hetero)aryl Methylene Isoxazole‐5(4H)‐One

Abstract 3‐methyl‐4‐(hetero)arylmethylidene isoxazole‐5(4H)‐one derivatives (4a‐r) derivatives (4a‐r) were synthesized by the multi‐component reactions. The multi‐component reactions (MCRs) of hydroxylamine hydrochloride, ethyl acetoacetate and aromatic/ heteroaromatic aldehyde catalyzed by novel Glutamic acid (Glu) as a biodegradable and eco‐friendly organocatalyst in ethanol on oil bath stirring at 60 °C. The final product homogeneity was examined by various spectroscopic techniques. In this work prepared compounds 4 q and 4 r are novel derivatives. The molecular dynamics of total energy and energy gap was calculated using DFT/B3LYP/6–31G (dp) method. The selected derivatives ( 4 l – r ) screened against in vitro MCF‐7 breast cancer cell line by MTT assay, derivatives 4 l and 4 o displayed very good activity with IC 50 of 6.57±2.31 , and 21.93±1.34 as compared to doxorubicin of IC 50 ( 3.69±0.17 ). Molecular docking studies were performed to evaluate interaction of PDB id: 1 M17 with led molecules of MCF‐7. Later, 1 M17 and 4 l underwent 200 ns molecular dynamics and simulation within physiological conditions, the outcomes showed that during the simulation, the ligand stayed in the same form. Further, the selected derivatives drug like computed using swissADME, and derivatives 4 l – r obeyed rule of Lipinski's. Furthermore, selected derivatives tested for electrochemical behavior using cyclic voltammetry, and compound 4 l and 4 q showed strong oxidation and reduction potential, thus these derivatives can present better antioxidant properties.