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

Saleem F., Shamim F., Özil M., Baltaş N., Salar U., Ashraf S., ...More

Future medicinal chemistry, vol.15, no.15, pp.1343-1368, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 15
  • Publication Date: 2023
  • Doi Number: 10.4155/fmc-2023-0073
  • Journal Name: Future medicinal chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.1343-1368
  • Keywords: in silico, in vitro, kinetic studies, pyridine, α-amylase activity, α-glucosidase activity
  • Recep Tayyip Erdoğan University Affiliated: Yes

Abstract

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) were 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 IC50 values of 0.15 ± 0.01 and 1.10 ± 0.04 μM, and a Km 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.