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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Main Authors:	Somaye Karimian, Yasaman Moghdani, Mahsima Khoshneviszadeh, Somayeh Pirhadi, Aida Iraji, Mehdi Khoshneviszadeh
Format:	Article
Language:	English
Published:	Hindawi Limited 2021-01-01
Series:	Journal of Chemistry
Online Access:	http://dx.doi.org/10.1155/2021/6664756

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spelling	doaj-15a9815137694439bc6e597f5e10ffa52021-03-08T02:00:57ZengHindawi LimitedJournal of Chemistry2090-90712021-01-01202110.1155/2021/6664756Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase InhibitorsSomaye Karimian0Yasaman Moghdani1Mahsima Khoshneviszadeh2Somayeh Pirhadi3Aida Iraji4Mehdi Khoshneviszadeh5Department of Medicinal ChemistryDepartment of Medicinal ChemistryMedicinal and Natural Products Chemistry Research CenterMedicinal and Natural Products Chemistry Research CenterMedicinal and Natural Products Chemistry Research CenterDepartment of Medicinal ChemistryIn 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.http://dx.doi.org/10.1155/2021/6664756
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Somaye Karimian Yasaman Moghdani Mahsima Khoshneviszadeh Somayeh Pirhadi Aida Iraji Mehdi Khoshneviszadeh
spellingShingle	Somaye Karimian Yasaman Moghdani Mahsima Khoshneviszadeh Somayeh Pirhadi Aida Iraji Mehdi Khoshneviszadeh Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors Journal of Chemistry
author_facet	Somaye Karimian Yasaman Moghdani Mahsima Khoshneviszadeh Somayeh Pirhadi Aida Iraji Mehdi Khoshneviszadeh
author_sort	Somaye Karimian
title	Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors
title_short	Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors
title_full	Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors
title_fullStr	Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors
title_full_unstemmed	Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors
title_sort	rational design, synthesis, in vitro, and in silico studies of dihydropyrimidinone derivatives as β-glucuronidase inhibitors
publisher	Hindawi Limited
series	Journal of Chemistry
issn	2090-9071
publishDate	2021-01-01
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.
url	http://dx.doi.org/10.1155/2021/6664756
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Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors

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