Synthesis, density functional theory and kinetic studies of aminopyridine based α-glucosidase inhibitors

  • Future Med Chem. 2023 Oct;15(19):1757-1772. doi: 10.4155/fmc-2023-0123.
Fazila Rizvi  1 ,  Raheel Ahmed  1 ,  Muhammad Arslan Bashir  1 ,  Saeed Ullah  1 ,  Humaira Zafar  2 ,  Atia-Tul-Wahab  2 ,  Hina Siddiqui  1 ,  Muhammad Iqbal Choudhary  1  2  3  4
Affiliations
  • 1. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • 2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • 3. Department of Biochemistry, King Abdul Aziz University, Jeddah, 21452, Saudi Arabia.
  • 4. Department of Chemistry, Faculty of Science and Technology, University of Airlangga, Komplek Campus C, Surabaya, 60115, Indonesia.
PMID: 37842772 DOI: 10.4155/fmc-2023-0123
Abstract

Aims: The current study aimed to develop new thiourea derivatives as potential α-glucosidase inhibitors for the management of hyperglycemia in patients of Type 2 diabetes, with a focus on identifying safer and more effective antidiabetic agents. Materials & methods: New thiourea derivatives (1-16) were synthesized through single-step chemical transformation and evaluated for in vitro α-glucosidase inhibition. Kinetic studies identified the mode of inhibition, free energy and type of interactions were analyzed through density functional theory and molecular docking. Results & conclusion: Compound 5 was identified as the most potent, noncompetitive and noncytotoxic inhibitor of α-glucosidase enzyme with a half-maximal inhibitory concentration of 24.62 ± 0.94 μM. Computational studies reinforce experimental results, demonstrating significant enzyme interactions via hydrophobic and π-π stacking forces.

Keywords
2-amino-5-(trifluoromethyl) pyridine; 2-aminopyridine; cytotoxicity; diabetes; α-glucosidase.
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