Design and synthesis of novel pyrazole-phenyl semicarbazone derivatives as potential α-glucosidase inhibitor: Kinetics and molecular dynamics simulation study

Azimi, F. and Ghasemi, J.B. and Azizian, H. and Najafi, M. and Faramarzi, M.A. and Saghaei, L. and Sadeghi-aliabadi, H. and Larijani, B. and Hassanzadeh, F. and 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. pp. 1082-1095.

Full text not available from this repository.
Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

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

Item Type: Article
Additional Information: cited By 1
Subjects: QT Physiology
Depositing User: eprints admin
Date Deposited: 18 Apr 2021 09:06
Last Modified: 18 Apr 2021 09:06
URI: http://eprints.iums.ac.ir/id/eprint/33337

Actions (login required)

View Item View Item
Iran University of Medical Sciences Scientific Repository is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.