Synthesis and bio-evaluation of newer dihydropyridines and tetrahydropyridines based glycomimetic azasugars.

ABSTRACT

This study presents the synthesis and bio-evaluation of new triazolylated dihydropyridine and tetrahydropyridine azasugar scaffolds (F1-14). Azasugar glycomimetics are the synthetic substances that mimic the structural and functional characteristics of natural carbohydrates showcasing promising potential as therapeutic agents for diabetes. The α-glucosidase inhibitory activity of synthesized final compounds were evaluated against the commercially available α-glucosidase enzyme. Majority of the screened compounds displayed excellent inhibition with IC50 values ranging from 2.12 to 75.11 µM, when compared to the standard drug Acarbose. Particularly, compound F5 with IC50 value of 2.12 µM was found to be the most active compound among the series. Further molecular docking studies of selected ligands were performed to investigate the binding interactions with enzyme active sites. Their specific binding patterns have been analysed with the binding sites of Saccharomyces cerevisiae α-glucosidase. These findings suggest these candidates as the potential leads for the anti-diabetic activity.