Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors

In the current study, a series of dihydropyrimidinone derivatives were rationally designed as β-glucuronidase inhibitors. These designed compounds were successfully synthesized and characterized through various spectroscopic techniques such as IR, 1H-NMR, 13C-NMR, and EI-MS. A structure-activity rel...

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Bibliographic Details
Published in:	Journal of chemistry Vol. 2021; pp. 1 - 10
Main Authors:	Karimian, Somaye, Moghdani, Yasaman, Khoshneviszadeh, Mahsima, Pirhadi, Somayeh, Iraji, Aida, Khoshneviszadeh, Mehdi
Format:	Journal Article
Language:	English
Published:	New York Hindawi 26-02-2021 John Wiley & Sons, Inc Hindawi Limited
Subjects:	Binding sites Comparative analysis Enzymes Glucaric acid Inhibitors Molecular docking Molecular dynamics NMR Nuclear magnetic resonance Synthesis
Online Access:	Get full text
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Summary:	In the current study, a series of dihydropyrimidinone derivatives were rationally designed as β-glucuronidase inhibitors. These designed compounds were successfully synthesized and characterized through various spectroscopic techniques such as IR, 1H-NMR, 13C-NMR, and EI-MS. A structure-activity relationship (SAR) of synthesized derivatives to inhibit β-glucuronidase was also established. In vitro biological evaluations revealed that 4i as the most potent compound in this series has an IC50 value of 31.52 ± 2.54 μM compared to the standard D-saccharic acid 1,4-lactone (IC50 = 41.32 ± 1.82 µM). Also, molecular docking and dynamics studies of the most potent compound are performed to evaluate interactions between the active compound and binding site.
ISSN:	2090-9063 2090-9071
DOI:	10.1155/2021/6664756