2. Academic Validation
  3. Chroman, pyridine, and coumarin in a new fused scaffold as α-glucosidase inhibitor: synthesis of new derivatives, in vitro, and in silico evaluations

Chroman, pyridine, and coumarin in a new fused scaffold as α-glucosidase inhibitor: synthesis of new derivatives, in vitro, and in silico evaluations

  • Bioorg Chem. 2025 Nov:166:109139. doi: 10.1016/j.bioorg.2025.109139.
Seyed Mohammad Hossein Pourmand 1,  Mohammad Halimi 2,  AmirHossein Alaeddini 3,  Mosayeb Akbari 1,  Milad Noori 1,  Somayeh Mojtabavi 4,  Mohammad Ali Faramarzi 4,  Maryam Mohammadi-Khanaposhtani 5,  Bagher Larijani 1,  Armin Dadgar 6,  Mohammad Mahdavi 7
Affiliations

Affiliations

  • 1 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Department of Biology, Babol Branch, Islamic Azad University, Babol, Iran.
  • 3 School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
  • 4 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 5 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  • 6 Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].
  • 7 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].
PMID: 41167059 DOI: 10.1016/j.bioorg.2025.109139
Abstract

Due to the presence of pyridine, coumarin, and chroman heterocycles in the potent α-glucosidase inhibitors, here, these heterocycles were fused together and 14 derivatives 8a-n were synthesized of this fused structure. After synthesis, new chroman-pyridine-coumarin derivatives 8a-n were evaluated against yeast form of α-glucosidase and after determination of the most potent compound, kinetic study was performed on it. In vitro enzymatic inhibition assay showed that all the new compounds 8a-n were more potent than used standard inhibitor (acarbose) and the most potent compounds, were compounds 8e and 8d with inhibitory activities around 20.7 folds more than standard inhibitor. In vitro kinetic study demonstrated that these compounds, like standard inhibitor, were competitive inhibitors. In silico docking and dynamics studies on the most potent compounds showed that these compounds formed stable complexes with the active site of α-glucosidase.

Keywords

Chroman; Coumarin; In silico; In vitro; Pyridine; α-glucosidase.

Figures
Products