Multicomponent diastereoselective synthesis of tetrahydropyridines as α-amylase and α-glucosidase enzymes inhibitors.

Background: Researchers seeking new drug candidates to treat diabetes mellitus have been exploring bioactive molecules found in nature, particularly tetrahydropyridines (THPs). Methods: A library of THPs 1-31 was synthesized via a one-pot multicomponent reaction and investigated for their inhibition potential against α-glucosidase and α-amylase enzymes. Results: A nitrophenyl-substituted compound 5 with IC 50 values of 0.15 ± 0.01 and 1.10 ± 0.04 μM, and a K m value of 1.30 mg/ml was identified as the most significant α-glucosidase and α-amylase inhibitor, respectively. Kinetic studies revealed the competitive mode of inhibition, and docking studies revealed that compound 5 binds to the enzyme by establishing hydrophobic and hydrophilic interactions and a salt bridge interaction with His279. Conclusion: These molecules may be a potential drug candidate for diabetes in the future.