Chromone-isoxazole hybrids molecules: synthesis, spectroscopic, MEDT, ELF, antibacterial, ADME-Tox, molecular docking and MD simulation investigations.

A mechanistic study was performed within the molecular electron density theory at the B3LYP/6-311G (d,p) computational level to explain the regioselectivity observed. An electron localization function analysis was also performed, and the results confirm the zwitterionic-type (zw-type) mechanism of the cycloaddition reactions between nitrile oxide and alkylated 4-chromene-2-carboxylate derivatives and shed more light on the obtained regioselectivity experimentally. studies on the pharmacokinetics, ADME and toxicity tests of the compounds were also performed, and it was projected that compounds , , and are pharmacokinetic and have favorable ADME profiles. Moreover, docking and molecular dynamics investigations were conducted to evaluate the interactions, orientation and conformation of the target compounds on the active sites of four distinct enzymes. The results of this investigation showed that two compounds, and , interacted effectively with the active site while maintaining acceptable binding energy.Communicated by Ramaswamy H. Sarma.