Synthetic piperidine-substituted chalcones as potential hits for α-amylase inhibitory and antioxidant activities.

Background: In medicinal chemistry, searching for new therapeutic entities to treat diabetes mellitus is of great concern. The piperidinyl-substituted chalcone scaffold has piqued our interest as a potential antidiabetic agent. Methods: A variety of piperidinyl-substituted chalcones 2-28 were synthesized and tested for α-amylase inhibitory and 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino- bis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activities. Results: Compared with the standard acarbose, all compounds inhibited α-amylase, with IC 50 values of 9.86-35.98 μM. Docking studies revealed an important binding interaction with the enzyme's catalytic site. The compounds also demonstrated promising radical-scavenging potential against  2,2-diphenyl-1-picrylhydrazyl and  2,2'-azino- bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals. Conclusion: This study has identified potential lead candidates for further advanced research searching for antidiabetic agents.