Synthesis, in vitro and in silico studies of naphto-1,3-oxazin-3(2H)-one derivatives as promising inhibitors of cholinesterase and α-glucosidase

Abstract Various substituted naphto-1,3-oxazin-3(2H)-one derivatives have been prepared by a three-component one-pot condensation reaction of 2-naphthol, aromatic aldehydes, and urea using phenylboronic acid as catalyst. The molecular structures of the synthesized compounds were characterized by physical and spectroscopic techniques and, for compound 4b, by single crystal X-ray diffraction analysis. The cholinesterase and α-glucosidase inhibitory activities of the titled compounds have been investigated in vitro. The obtained results revealed that some of the synthesized compounds are highly active towards both AChE/BChE and α-Glucosidase with IC50 values lower than those of the standards galanthamine and acarbose. In Silico studies such as Hirshfeld surface, docking study, DFT calculations, and ADME properties have been also performed in order to get insights into the molecular structure, chemical reactivity, structure-activity relationship, and bioavailability of the synthesized compounds.