Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor

Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor Publisher Pubmed

Azimi F¹ ; Azizian H² ; Najafi M³ ; Khodarahmi G⁴ ; Saghaei L⁴ ; Hassanzadeh M⁴ ; Ghasemi JB⁵ ; Faramarzi MA⁶ ; Larijani B⁷ ; Hassanzadeh F⁴ ; Mahdavi M⁷

Show Affiliations

1. Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran
2. Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Science, Tehran, Iran
3. Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Iran
4. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Science, Hezar Jerib, 817416-73461, Isfahan, Iran
5. School of Chemistry, University College of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran
6. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, 1417614411, Iran
7. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Scientific Reports Published:2021

Abstract

In this work, new derivatives of biphenyl pyrazole-benzofuran hybrids were designed, synthesized and evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase activity. Newly identified inhibitors were found to be four to eighteen folds more active with IC50 values in the range of 40.6 ± 0.2–164.3 ± 1.8 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 10.0 μM). Limited Structure-activity relationship was established. A kinetic binding study indicated that most active compound 8e acted as the competitive inhibitors of α-glucosidase with Ki = 38 μM. Molecular docking has also been performed to find the interaction modes responsible for the desired inhibitory activity. As expected, all pharmacophoric features, used in the design of the hybrid, are involved in the interaction with the active site of the enzyme. In addition, molecular dynamic simulations showed compound 8e oriented vertically into the active site from mouth to the bottom and stabilized the enzyme domains by interacting with the interface of domain A and domain B and the back side of the active site while acarbose formed non-binding interaction with the residue belong to the domain A of the enzyme. © 2021, The Author(s).

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Style	Citing Format
MLA	Azimi F, et al.. "Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor." Scientific Reports, vol. 11, no. 1, 2021, pp. -.
APA	Azimi F, Azizian H, Najafi M, Khodarahmi G, Saghaei L, Hassanzadeh M, Ghasemi JB, Faramarzi MA, Larijani B, Hassanzadeh F, Mahdavi M (2021). Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor. Scientific Reports, 11(1), -.
Chicago	Azimi F, Azizian H, Najafi M, Khodarahmi G, Saghaei L, Hassanzadeh M, Ghasemi JB, et al.. "Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor." Scientific Reports 11, no. 1 (2021): -.
Harvard	Azimi F et al. (2021) 'Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor', Scientific Reports, 11(1), pp. -.
Vancouver	Azimi F, Azizian H, Najafi M, Khodarahmi G, Saghaei L, Hassanzadeh M, et al.. Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor. Scientific Reports. 2021;11(1):-.
BibTex	@article{ author = {Azimi F and Azizian H and Najafi M and Khodarahmi G and Saghaei L and Hassanzadeh M and Ghasemi JB and Faramarzi MA and Larijani B and Hassanzadeh F and Mahdavi M}, title = {Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor}, journal = {Scientific Reports}, volume = {11}, number = {1}, pages = {-}, year = {2021} }
RIS	TY - JOUR AU - Azimi F AU - Azizian H AU - Najafi M AU - Khodarahmi G AU - Saghaei L AU - Hassanzadeh M AU - Ghasemi JB AU - Faramarzi MA AU - Larijani B AU - Hassanzadeh F AU - Mahdavi M TI - Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor JO - Scientific Reports VL - 11 IS - 1 SP - EP - PY - 2021 ER -

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