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

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 a-glucosidase and a-amylase enzymes. Results: A nitrophenyl-substituted compound 5 with IC50 values of 0.15 +/- 0.01 and 1.10 +/- 0.04 mu M, and a K-m value of 1.30 mg/ml was identified as the most significant alpha-glucosidase and alpha-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.

Automated summary

In this study, a library of tetrahydropyridine (THP) compounds was synthesized and investigated for their potential as drug candidates for diabetes treatment. One compound with nitrophenyl substitution was identified as a strong inhibitor of α-glucosidase and α-amylase enzymes. Docking studies revealed its binding mechanism with the enzymes.