2. Academic Validation
  3. Pyrano[2,3-b]chromone derivatives as novel dual inhibitors of α-glucosidase and α-amylase: Design, synthesis, biological evaluation, and in silico studies

Pyrano[2,3-b]chromone derivatives as novel dual inhibitors of α-glucosidase and α-amylase: Design, synthesis, biological evaluation, and in silico studies

  • Bioorg Chem. 2024 Apr:145:107207. doi: 10.1016/j.bioorg.2024.107207.
Elnaz Farzaneh 1,  Mohammad Mohammadi 2,  Pooya Raymand 3,  Milad Noori 3,  Sahand Golestani 2,  Sara Ranjbar 4,  Younes Ghasemi 5,  Maryam Mohammadi-Khanaposhtani 6,  Mehdi Asadi 7,  Ensieh Nasli Esfahani 8,  Hossein Rastegar 9,  Bagher Larijani 3,  Mohammad Mahdavi 10,  Parham Taslimi 11
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
  • 2 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 3 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 4 Computational Vaccine and Drug Design Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 5 Computational Vaccine and Drug Design Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Iran.
  • 6 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  • 7 Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Iran.
  • 8 Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 9 Cosmetic Products Research Center, Iranian Food and Drug Administration, MOHE, Tehran, Iran.
  • 10 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].
  • 11 Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Türkiye. Electronic address: [email protected].
PMID: 38402795 DOI: 10.1016/j.bioorg.2024.107207
Abstract

Inhibition of α-glucosidase and α-amylase is an important target for treatment of type 2 diabetes. In this work, a novel series of pyrano[2,3-b]chromene derivatives 5a-m was designed based on potent α-glucosidase and α-amylase inhibitors and synthesized by simple chemical reactions. These compounds were evaluated against the latter enzymes. Most of the title compounds exhibited high inhibitory activity against α-glucosidase and α-amylase in comparison to standard inhibitor (acarbose). Representatively, the most potent compound, 4-methoxy derivative 5d, was 30.4 fold more potent than acarbose against α-glucosidase and 6.1 fold more potent than this drug against α-amylase. In silico molecular modeling demonstrated that compound 5d attached to the active sites of α-glucosidase and α-amylase with a favorable binding energies and established interactions with important Amino acids. Dynamics of compound 5d also showed that this compound formed a stable complex with the α-glucosidase active site. In silicodrug-likeness as well as ADMET prediction of this compound was also performed and satisfactory results were obtained.

Keywords

ADMET; Diabetes; Docking; Pyrano[2,3-b]chromene; α-Amylase; α-Glucosidase.

Figures
Products