Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study

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Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study Publisher Pubmed

Azimi F¹ ; Ghasemi JB² ; Azizian H³ ; Najafi M⁴ ; Faramarzi MA⁵ ; Saghaei L¹ ; Sadeghialiabadi H¹ ; Larijani B⁶ ; Hassanzadeh F¹ ; Mahdavi M⁶

Show Affiliations

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

Source: International Journal of Biological Macromolecules Published:2021

Abstract

A series of novel pyrazole-phenyl semicarbazone derivatives were designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. Given the importance of hydrogen bonding in promoting the α-glucosidase inhibitory activity, pharmacophore modification was established. The docking results rationalized the idea of the design. All newly synthesized compounds exhibited excellent in vitro yeast α-glucosidase inhibition (IC50 values in the range of 65.1–695.0 μM) even much more potent than standard drug acarbose (IC50 = 750.0 μM). Among them, compounds 8o displayed the most potent α-glucosidase inhibitory activity (IC50 = 65.1 ± 0.3 μM). Kinetic study of compound 8o revealed that it inhibited α-glucosidase in a competitive mode (Ki = 87.0 μM). Limited SAR suggested that electronic properties of substitutions have little effect on inhibitory potential of compounds. Cytotoxic studies demonstrated that the active compounds (8o, 8k, 8p, 8l, 8i, and 8a) compounds are also non-cytotoxic. The binding modes of the most potent compounds 8o, 8k, 8p, 8l and 8i was studied through in silico docking studies. Molecular dynamic simulations have been performed in order to explain the dynamic behavior and structural changes of the systems by the calculation of the root mean square deviation (RMSD) and root mean square fluctuation (RMSF). © 2020

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Style	Citing Format
MLA	Azimi F, et al.. "Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study." International Journal of Biological Macromolecules, vol. 166, no. , 2021, pp. 1082-1095.
APA	Azimi F, Ghasemi JB, Azizian H, Najafi M, Faramarzi MA, Saghaei L, Sadeghialiabadi H, Larijani B, Hassanzadeh F, Mahdavi M (2021). Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study. International Journal of Biological Macromolecules, 166(), 1082-1095.
Chicago	Azimi F, Ghasemi JB, Azizian H, Najafi M, Faramarzi MA, Saghaei L, Sadeghialiabadi H, Larijani B, Hassanzadeh F, Mahdavi M. "Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study." International Journal of Biological Macromolecules 166, no. (2021): 1082-1095.
Harvard	Azimi F et al. (2021) 'Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study', International Journal of Biological Macromolecules, 166(), pp. 1082-1095.
Vancouver	Azimi F, Ghasemi JB, Azizian H, Najafi M, Faramarzi MA, Saghaei L, et al.. Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study. International Journal of Biological Macromolecules. 2021;166():1082-1095.
BibTex	@article{ author = {Azimi F and Ghasemi JB and Azizian H and Najafi M and Faramarzi MA and Saghaei L and Sadeghialiabadi H and Larijani B and Hassanzadeh F and Mahdavi M}, title = {Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study}, journal = {International Journal of Biological Macromolecules}, volume = {166}, number = {}, pages = {1082-1095}, year = {2021} }
RIS	TY - JOUR AU - Azimi F AU - Ghasemi JB AU - Azizian H AU - Najafi M AU - Faramarzi MA AU - Saghaei L AU - Sadeghialiabadi H AU - Larijani B AU - Hassanzadeh F AU - Mahdavi M TI - Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study JO - International Journal of Biological Macromolecules VL - 166 IS - SP - 1082 EP - 1095 PY - 2021 ER -

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