Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors
A series of purin-6-one derivatives were synthesized, and their in vitro inhibitory activity against phosphodiesterase-2 (PDE2) was evaluated by using a fluorescence polarization assay. Three compounds, that are, 2j, 2p, and 2q, showed significant inhibitory activity against PDE2 with IC50 values of...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2016/6878353 |
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| author | Wei Yuan Xin-Yun Zhao Xi Chen Chang-Guo Zhan |
| author_facet | Wei Yuan Xin-Yun Zhao Xi Chen Chang-Guo Zhan |
| author_sort | Wei Yuan |
| collection | DOAJ |
| description | A series of purin-6-one derivatives were synthesized, and their in vitro inhibitory activity against phosphodiesterase-2 (PDE2) was evaluated by using a fluorescence polarization assay. Three compounds, that are, 2j, 2p, and 2q, showed significant inhibitory activity against PDE2 with IC50 values of 1.73, 0.18, and 3.43 μM, respectively. Structure-activity relationship (SAR) analysis was performed to explore the relationship between the chemical structures of these compounds and their inhibitory activity. Compounds 2j, 2p, and 2q were further selected for molecular docking study. The docking results suggested that these ligands bind with hydrophobic pockets of the catalytic active site of PDE2, where a Tyr655 residue was found to be important in binding with compound 2p, the most potent inhibitor identified in this study. Our present study provides useful information for the future design of novel PDE2 inhibitors. |
| format | Article |
| id | doaj-art-5938d668622149de8ed8ccd00d8efed8 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-5938d668622149de8ed8ccd00d8efed82025-02-03T01:11:31ZengWileyJournal of Chemistry2090-90632090-90712016-01-01201610.1155/2016/68783536878353Purin-6-One Derivatives as Phosphodiesterase-2 InhibitorsWei Yuan0Xin-Yun Zhao1Xi Chen2Chang-Guo Zhan3College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan 430074, ChinaCollege of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan 430074, ChinaCollege of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan 430074, ChinaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone, Lexington, KY 40536, USAA series of purin-6-one derivatives were synthesized, and their in vitro inhibitory activity against phosphodiesterase-2 (PDE2) was evaluated by using a fluorescence polarization assay. Three compounds, that are, 2j, 2p, and 2q, showed significant inhibitory activity against PDE2 with IC50 values of 1.73, 0.18, and 3.43 μM, respectively. Structure-activity relationship (SAR) analysis was performed to explore the relationship between the chemical structures of these compounds and their inhibitory activity. Compounds 2j, 2p, and 2q were further selected for molecular docking study. The docking results suggested that these ligands bind with hydrophobic pockets of the catalytic active site of PDE2, where a Tyr655 residue was found to be important in binding with compound 2p, the most potent inhibitor identified in this study. Our present study provides useful information for the future design of novel PDE2 inhibitors.http://dx.doi.org/10.1155/2016/6878353 |
| spellingShingle | Wei Yuan Xin-Yun Zhao Xi Chen Chang-Guo Zhan Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors Journal of Chemistry |
| title | Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors |
| title_full | Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors |
| title_fullStr | Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors |
| title_full_unstemmed | Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors |
| title_short | Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors |
| title_sort | purin 6 one derivatives as phosphodiesterase 2 inhibitors |
| url | http://dx.doi.org/10.1155/2016/6878353 |
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