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

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):

Share this content! By

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

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

Related Docs

View other Related Docs

1. Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor, Scientific Reports (2021)

2. Design and Synthesis of Novel Quinazolinone-Pyrazole Derivatives As Potential Α-Glucosidase Inhibitors: Structure-Activity Relationship, Molecular Modeling and Kinetic Study, Bioorganic Chemistry (2021)

3. In Silico and in Vitro Studies of Thiosemicarbazone-Indole Hybrid Compounds As Potent Α-Glycosidase Inhibitors, Computational Biology and Chemistry (2022)

Experts (# of related papers)

View all Related Experts

Farshid Hassanzadeh (6)

Mustafa Ghanadian (4)

Other Related Docs

4. New Thiosemicarbazide-1,2,3-Triazole Hybrids As Potent Α-Glucosidase Inhibitors: Design, Synthesis, and Biological Evaluation, Journal of Molecular Structure (2019)

5. Design, Synthesis, and Evaluation of Triazolo[1,5-A]Pyridines As Novel and Potent Α‑Glucosidase Inhibitors, Scientific Reports (2025)

6. Kinetic Studies, Molecular Docking, and Antioxidant Activity of Novel 1,3-Diphenyl Pyrazole-Thiosemicarbazone With Anti-Tyrosinase and Anti-Melanogenesis Properties, Bioorganic Chemistry (2024)

7. Drug Repurposing for Diabetes Mellitus: In Silico and in Vitro Investigation of Drugbank Database for Α-Glucosidase Inhibitors, International Journal of Biological Macromolecules (2024)

8. Validated Qsar Analysis of Some Diaryl Substituted Pyrazoles As Ccr2 Inhibitors by Various Linear and Nonlinear Multivariate Chemometrics Methods, European Journal of Medicinal Chemistry (2010)

9. In Silico Analysis of Transmembrane Protein 31 (Tmem31)Antigen to Design Novel Multiepitope Peptide and Dna Cancer Vaccines Against Melanoma, Molecular Immunology (2019)

10. Designing and Characterization of Tregitope-Based Multi-Epitope Vaccine Against Multiple Sclerosis: An Immunoinformatic Approach, Current Drug Safety (2023)

11. The Inhibitory Potential of Natural Compounds on Α-Amylase and Α-Glucosidase in the Management of Type 2 Diabetes, Iranian Journal of Chemistry and Chemical Engineering (2024)

12. Hybrid Pharmacophore Design, Molecular Docking, Synthesis, and Biological Evaluation of Novel Aldimine-Type Schiff Base Derivatives As Tubulin Polymerization Inhibitor, Chemistry and Biodiversity (2018)

13. Synthesis, Antimicrobial Evaluation and Docking Studies of Some Novel Quinazolinone Schiff Base Derivatives, Research in Pharmaceutical Sciences (2018)

14. Synthesis, Qsar Modeling, and Molecular Docking Studies of 1,2,3-Triazole-Pyrazole Hybrids As Significant Anti-Cancer and Anti-Microbial Agents, Journal of Molecular Structure (2025)

15. Design of Multivalent-Epitope Vaccine Models Directed Toward the World’S Population Against Hiv-Gag Polyprotein: Reverse Vaccinology and Immunoinformatics, PLoS ONE (2024)

16. Docking Study, Synthesis and Antimicrobial Evaluation of Some Novel 4-Anilinoquinazoline Derivatives, Research in Pharmaceutical Sciences (2017)

17. Inhibitory Effect of Flavonoid Glycosides on Digestive Enzymes: In Silico, in Vitro, and in Vivo Studies, International Journal of Biological Macromolecules (2022)

18. Exploring the Inhibitory Properties of Biflavonoids on Α-Glucosidase; Computational and Experimental Approaches, International Journal of Biological Macromolecules (2023)

19. In Silico and in Vivo Studies of Truncated Forms of Flagellin (Flic) of Enteroaggregative Escherichia Coli Fused to Fimh From Uropathogenic Escherichia Coli As a Vaccine Candidate Against Urinary Tract Infections, Journal of Biotechnology (2014)

20. Synthesis, and Molecular Docking Studies of Novel 1,2,3-Triazoles-Linked Pyrazole Carboxamides As Significant Anti-Microbial and Anti-Cancer Agents, Results in Chemistry (2024)

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 -

Science Communicator Platform

Authors

Abstract