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Pyrano[2,3-B]Chromone Derivatives As Novel Dual Inhibitors of Α-Glucosidase and Α-Amylase: Design, Synthesis, Biological Evaluation, and in Silico Studies Publisher Pubmed



Farzaneh E1 ; Mohammadi M2 ; Raymand P3 ; Noori M3 ; Golestani S2 ; Ranjbar S4, 5 ; Ghasemi Y4, 5, 6 ; Mohammadikhanaposhtani M7 ; Asadi M8 ; Nasli Esfahani E9 ; Rastegar H10 ; Larijani B3 ; Mahdavi M3 ; Taslimi P11
Authors
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  2. 2. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Computational Vaccine and Drug Design Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  6. 6. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Iran
  7. 7. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  8. 8. Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Iran
  9. 9. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Cosmetic Products Research Center, Iranian Food and Drug Administration, MOHE, Tehran, Iran
  11. 11. Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkey

Source: Bioorganic Chemistry Published:2024


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 silico drug-likeness as well as ADMET prediction of this compound was also performed and satisfactory results were obtained. © 2024 Elsevier Inc.
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