Pyrano[2,3-b]chromone derivatives as novel dual inhibitors of α-glucosidase and α-amylase: Design, synthesis, biological evaluation, and in silico studies
Elnaz Farzaneh, Mohammad Hossein Mohammadi, Pooya Raymand, Milad Noori, Sahand Golestani, Sara Ranjbar, Younes Ghasemi, Maryam Mohammadi‐Khanaposhtani, Mehdi Asadi, Ensieh Nasli‐Esfahani, Hossein Rastegar, Bagher Larijani, Mohammad Mahdavi, Parham Taslımı
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.