Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 Inhibitors
Human sirtuin 2 (SIRT2), a member of the sirtuin family, has been considered as a promising drug target in cancer, neurodegenerative diseases, type II diabetes, and bacterial infections. Thus, SIRT2 inhibitors have been involved in effective treatment strategies for related diseases. Using previousl...
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| Format: | Article |
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MDPI AG
2019-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/15/2724 |
| _version_ | 1819207054427947008 |
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| author | Lijiao Wang Chao Li Wei Chen Chen Song Xing Zhang Fan Yang Chen Wang Yuanyuan Zhang Shan Qian Zhouyu Wang Lingling Yang |
| author_facet | Lijiao Wang Chao Li Wei Chen Chen Song Xing Zhang Fan Yang Chen Wang Yuanyuan Zhang Shan Qian Zhouyu Wang Lingling Yang |
| author_sort | Lijiao Wang |
| collection | DOAJ |
| description | Human sirtuin 2 (SIRT2), a member of the sirtuin family, has been considered as a promising drug target in cancer, neurodegenerative diseases, type II diabetes, and bacterial infections. Thus, SIRT2 inhibitors have been involved in effective treatment strategies for related diseases. Using previously established fluorescence-based assays for SIRT2 activity tests, the authors screened their in-house database and identified a compound, 4-(5-((3-(quinolin-5-yl)ureido)methyl)furan-2-yl)benzoic acid (<b>20</b>), which displayed 63 ± 5% and 35 ± 3% inhibition against SIRT2 at 100 μM and 10 μM, respectively. The structure-activity relationship (SAR) analyses of a series of synthesized (5-phenylfuran-2-yl)methanamine derivatives led to the identification of a potent compound <b>25</b> with an IC<sub>50</sub> value of 2.47 μM, which is more potent than AGK2 (IC<sub>50</sub> = 17.75 μM). Meanwhile, <b>25</b> likely possesses better water solubility (cLogP = 1.63 and cLogS = −3.63). Finally, the molecular docking analyses indicated that <b>25</b> fitted well with the induced hydrophobic pocket of SIRT2. |
| first_indexed | 2024-12-23T05:17:24Z |
| format | Article |
| id | doaj.art-4e96a5f531b44404a5db66b3b2a223ed |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-23T05:17:24Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-4e96a5f531b44404a5db66b3b2a223ed2022-12-21T17:58:47ZengMDPI AGMolecules1420-30492019-07-012415272410.3390/molecules24152724molecules24152724Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 InhibitorsLijiao Wang0Chao Li1Wei Chen2Chen Song3Xing Zhang4Fan Yang5Chen Wang6Yuanyuan Zhang7Shan Qian8Zhouyu Wang9Lingling Yang10College of Food and Bioengineering, Xihua University, Sichuan 610039, ChinaCollege of Food and Bioengineering, Xihua University, Sichuan 610039, ChinaCollege of Food and Bioengineering, Xihua University, Sichuan 610039, ChinaCollege of Food and Bioengineering, Xihua University, Sichuan 610039, ChinaCollege of Science, Xihua University, Sichuan 610039, ChinaCollege of Food and Bioengineering, Xihua University, Sichuan 610039, ChinaCollege of Food and Bioengineering, Xihua University, Sichuan 610039, ChinaCollege of Science, Xihua University, Sichuan 610039, ChinaCollege of Food and Bioengineering, Xihua University, Sichuan 610039, ChinaCollege of Science, Xihua University, Sichuan 610039, ChinaCollege of Food and Bioengineering, Xihua University, Sichuan 610039, ChinaHuman sirtuin 2 (SIRT2), a member of the sirtuin family, has been considered as a promising drug target in cancer, neurodegenerative diseases, type II diabetes, and bacterial infections. Thus, SIRT2 inhibitors have been involved in effective treatment strategies for related diseases. Using previously established fluorescence-based assays for SIRT2 activity tests, the authors screened their in-house database and identified a compound, 4-(5-((3-(quinolin-5-yl)ureido)methyl)furan-2-yl)benzoic acid (<b>20</b>), which displayed 63 ± 5% and 35 ± 3% inhibition against SIRT2 at 100 μM and 10 μM, respectively. The structure-activity relationship (SAR) analyses of a series of synthesized (5-phenylfuran-2-yl)methanamine derivatives led to the identification of a potent compound <b>25</b> with an IC<sub>50</sub> value of 2.47 μM, which is more potent than AGK2 (IC<sub>50</sub> = 17.75 μM). Meanwhile, <b>25</b> likely possesses better water solubility (cLogP = 1.63 and cLogS = −3.63). Finally, the molecular docking analyses indicated that <b>25</b> fitted well with the induced hydrophobic pocket of SIRT2.https://www.mdpi.com/1420-3049/24/15/2724histone deacetylasessirtuinsSIRT2SAR studiesmolecular docking |
| spellingShingle | Lijiao Wang Chao Li Wei Chen Chen Song Xing Zhang Fan Yang Chen Wang Yuanyuan Zhang Shan Qian Zhouyu Wang Lingling Yang Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 Inhibitors Molecules histone deacetylases sirtuins SIRT2 SAR studies molecular docking |
| title | Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 Inhibitors |
| title_full | Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 Inhibitors |
| title_fullStr | Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 Inhibitors |
| title_full_unstemmed | Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 Inhibitors |
| title_short | Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 Inhibitors |
| title_sort | discovery of 5 phenylfuran 2 yl methanamine derivatives as new human sirtuin 2 inhibitors |
| topic | histone deacetylases sirtuins SIRT2 SAR studies molecular docking |
| url | https://www.mdpi.com/1420-3049/24/15/2724 |
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