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: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2021/6664756 |
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| author | Somaye Karimian Yasaman Moghdani Mahsima Khoshneviszadeh Somayeh Pirhadi Aida Iraji Mehdi Khoshneviszadeh |
| author_facet | Somaye Karimian Yasaman Moghdani Mahsima Khoshneviszadeh Somayeh Pirhadi Aida Iraji Mehdi Khoshneviszadeh |
| author_sort | Somaye Karimian |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-15a9815137694439bc6e597f5e10ffa5 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-15a9815137694439bc6e597f5e10ffa52025-02-03T01:25:41ZengWileyJournal of Chemistry2090-90632090-90712021-01-01202110.1155/2021/66647566664756Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase InhibitorsSomaye Karimian0Yasaman Moghdani1Mahsima Khoshneviszadeh2Somayeh Pirhadi3Aida Iraji4Mehdi Khoshneviszadeh5Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, IranMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, IranMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranIn 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 |
| 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 |
| title | 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_short | 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 |
| url | http://dx.doi.org/10.1155/2021/6664756 |
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