Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents

Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents Publisher

Ghorbani H¹ ; Ebadi A² ; Faramarzi MA³ ; Mojtabavi S³ ; Mahdavi M⁴ ; Najafi Z¹

Show Affiliations

1. Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
2. Department of Medicinal Chemistry, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
3. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran
4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Molecular Structure Published:2023

Abstract

Some new coumarin-fused 4H-pyran derivatives were synthesized and assessed against yeast α-glucosidase enzyme. All of the synthesized compounds showed significant inhibitory activity towards the enzyme with IC50 values in range of 30.05 ± 0.5–274.3 ± 1.0 μM in comparison with acarbose, as a standard agent (IC50 = 750.0 μM). Among them, 4-(4-(4-bromobenzyloxy)-3-methoxyphenyl)-2-amino -4,5-dihydro-5-oxopyrano[3,2-c]chromene-3-carbonitrile (compound 6e) indicated the most potent inhibitory activity. The kinetic study of the compound 6e revealed that this compound inhibited α-glucosidase in a competitive pattern. Homology modeling was utilized to determine 3D structure of the α-glucoside enzyme. Afterwards, the molecular docking and dynamic simulation studies confirmed successful placement of the compound 6e in the active site of α-glucosidase. Besides, the R- and S- enantiomers of the compound 6e showed significant interactions with the catalytic triad residues (Asp214, Glu276, Asp349). The results of in silico prediction study for ADME also indicated that these coumarin-fused 4H-pyran derivatives have acceptable pharmacokinetic and potential therapeutic benefits for the future treatment of type 2 diabetes mellitus (T2DM). © 2023 Elsevier B.V.

2. Quinazolinone-Dihydropyrano[3,2-B]Pyran Hybrids As New Α-Glucosidase Inhibitors: Design, Synthesis, Enzymatic Inhibition, Docking Study and Prediction of Pharmacokinetic, Bioorganic Chemistry (2021)

3. Design, Synthesis and in Vitro Α-Glucosidase Inhibition of Novel Dihydropyrano[3,2-C]Quinoline Derivatives As Potential Anti-Diabetic Agents, Bioorganic Chemistry (2018)

4. Pyrano[2,3-B]Chromone Derivatives As Novel Dual Inhibitors of Α-Glucosidase and Α-Amylase: Design, Synthesis, Biological Evaluation, and in Silico Studies, Bioorganic Chemistry (2024)

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Mohammad Mahdavi (4)

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Style	Citing Format
MLA	Ghorbani H, et al.. "Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents." Journal of Molecular Structure, vol. 1284, no. , 2023, pp. -.
APA	Ghorbani H, Ebadi A, Faramarzi MA, Mojtabavi S, Mahdavi M, Najafi Z (2023). Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents. Journal of Molecular Structure, 1284(), -.
Chicago	Ghorbani H, Ebadi A, Faramarzi MA, Mojtabavi S, Mahdavi M, Najafi Z. "Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents." Journal of Molecular Structure 1284, no. (2023): -.
Harvard	Ghorbani H et al. (2023) 'Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents', Journal of Molecular Structure, 1284(), pp. -.
Vancouver	Ghorbani H, Ebadi A, Faramarzi MA, Mojtabavi S, Mahdavi M, Najafi Z. Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents. Journal of Molecular Structure. 2023;1284():-.
BibTex	@article{ author = {Ghorbani H and Ebadi A and Faramarzi MA and Mojtabavi S and Mahdavi M and Najafi Z}, title = {Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents}, journal = {Journal of Molecular Structure}, volume = {1284}, number = {}, pages = {-}, year = {2023} }
RIS	TY - JOUR AU - Ghorbani H AU - Ebadi A AU - Faramarzi MA AU - Mojtabavi S AU - Mahdavi M AU - Najafi Z TI - Synthesis, in Vitro Α-Glucosidase Inhibitory Activity and Molecular Dynamics Simulation of Some New Coumarin-Fused 4H-Pyran Derivatives As Potential Anti-Diabetic Agents JO - Journal of Molecular Structure VL - 1284 IS - SP - EP - PY - 2023 ER -

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