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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Published in:Journal of chemistry 2021-02, Vol.2021, p.1-10
Main Authors: Karimian, Somaye, Moghdani, Yasaman, Khoshneviszadeh, Mahsima, Pirhadi, Somayeh, Iraji, Aida, Khoshneviszadeh, Mehdi
Format: Article
Language:English
Subjects:
Binding sites
Comparative analysis
Enzymes
Glucaric acid
Inhibitors
Molecular docking
Molecular dynamics
NMR
Nuclear magnetic resonance
Synthesis
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description 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.
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subjects Binding sites
Comparative analysis
Enzymes
Glucaric acid
Inhibitors
Molecular docking
Molecular dynamics
NMR
Nuclear magnetic resonance
Synthesis
title Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors
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