Ultrasound Assisted Synthesis of Pyran Derivatives Catalysed by Uranyl Nitrate and Their Molecular Docking Against Glycogen Synthase Kinase-3 Beta Receptor

Abstract

Objective: Green and medicinal chemistry share the common objective of creating easy-to-use, cost-effective catalytic systems using commonly available materials. To synthesize 4H-pyrans derivatives by one-pot chemical reaction of cycloalkanones, substituted aldehyde with malononitrile at conventional, and ultrasonic method using uranyl nitrate hexahydrate acting as a catalyst were produced pyrans derivatives (IVa–IVj) in good to high yields. Methods: The main benefits of this eco-friendly approach are its high efficiency, solvent-free or low solvent reaction conditions, ease of operation, and utilization of readily available catalysts. After conducting additional research on the binding manner of the contacts between the most active frameworks and the α-glucosidase active sites, docking analysis was carried out to investigate the α-glucosidase enzyme’s active cavity. Results and Discussion: Upon interpreting the data, it became evident that scaffolds (IVa) and (IVc) were the most effective inhibitors of α-glucosidase, exhibiting excellent binding contacts with the enzyme’s active region. Conclusions: We propose a simple and green synthetic methodology for the synthesis of pyran derivatives and the molecular docking experiments showed that these compounds are strongly bound to the protein-binding sites of glycogen synthase kinase-3 beta receptor.