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

  • Future Med Chem. 2023 Aug;15(15):1343-1368. doi: 10.4155/fmc-2023-0073.
Faiza Saleem  1 ,  Fariha Shamim  1 ,  Musa Özil  2 ,  Nimet Baltaş  2 ,  Uzma Salar  3 ,  Sajda Ashraf  3 ,  Zaheer Ul-Haq  3 ,  Muhammad Taha  4 ,  Mehwish Solangi  1 ,  Khalid Mohammed Khan  1
Affiliations
  • 1. HEJ Research Institute of Chemistry, International Center for Chemical & Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • 2. Department of Chemistry, Recep Tayyip Erdogan University, 53100, Rize, Turkey.
  • 3. Dr Panjwani Center for Molecular Medicine & Drug Research, International Center for Chemical & Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • 4. Department of Clinical Pharmacy, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, PO Box 31441, Dammam, Saudi Arabia.
PMID: 37650736 DOI: 10.4155/fmc-2023-0073
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.

Keywords
in silico; in vitro; kinetic studies; pyridine; α-amylase activity; α-glucosidase activity.
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