Efficient synthesis and in-silico studies of pyrano[3,2-c]pyrones based glycohybrids

Abstract

This work is comprising of designing, efficient synthesis and molecular docking studies of pyrano[3,2-c]pyrones based stereodivergent glycohybrids. The diverse pyrano[3,2-c]pyrones based glycohybrids were efficiently prepared through condensation of 4-hydroxycoumarin derivatives and 4‑hydroxy-6-methyl-2H-pyran-2-ones with various enantiopure 2,3-dideoxy-α,β-unsaturated carbohydrate enals using organo-catalyst, L-proline, in EtOAc at room temperature. 3,4,6-tri-O-acetyl-D-glucal derived acetyl-protected carbohydrate enals yielded highly diastereoselective glycohybrid products. Whereas, poor selectivity was observed with α,β-unsaturated carbohydrate enals obtained from 3,4,6-tri-O-acetyl-D-galactal. The in-silico investigations show the significant binding activity of the selected compounds in the active binding site of HCK protein (PDB: 1QCF) with the better docking score of −7.13 kcal/mol as compared to the co-crystallized ligand PP1 (−6.77 kcal/mol). Additionally, MM/GBSA was calculated using the Prime module to determine the binding energy of the ligands. Selected compounds showed the maximum binding affinity of −74.18 kcal/mol compared to the co-crystallized ligand PP1 (−70.40 kcal/mol). ADMET screening of these compounds predicts the low toxicity and better metabolic profile of the synthesized compounds inside the body. © 2024 Elsevier B.V.