Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome
Twenty eight 7-substitued fangchinoline analogues, of which twenty two were novel, were synthesized and evaluated for their effect to inhibit lipopolysaccharide/nigericin (LPS/NIG)-induced IL-1β release at both cell and protein levels at the concentration of 5 μM. Among them, compo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/6/1154 |
| _version_ | 1819119916198920192 |
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| author | Ting Liu Qingxuan Zeng Xiaoqiang Zhao Wei Wei Yinghong Li Hongbin Deng Danqing Song |
| author_facet | Ting Liu Qingxuan Zeng Xiaoqiang Zhao Wei Wei Yinghong Li Hongbin Deng Danqing Song |
| author_sort | Ting Liu |
| collection | DOAJ |
| description | Twenty eight 7-substitued fangchinoline analogues, of which twenty two were novel, were synthesized and evaluated for their effect to inhibit lipopolysaccharide/nigericin (LPS/NIG)-induced IL-1β release at both cell and protein levels at the concentration of 5 μM. Among them, compound <b>6</b> exhibited promising inhibitory potency against IL-β activation with an IC<sub>50</sub> value of 3.7 μM. Preliminary mechanism study revealed that <b>6</b> might target NLRP3 protein, and then block ASC pyroptosome formation with-NLRP3, rather than acting on the activation of the NLRP3 inflammasome (NF-κB and MAPK pathways) or caspase-1 protein. Our current study supported the potential role of compound <b>6</b> against IL-β activation, and provided powerful information for developing fangchinoline derivatives into a novel class of anti-inflammatory agents. |
| first_indexed | 2024-12-22T06:12:22Z |
| format | Article |
| id | doaj.art-178a0955bea54001b9d1c978938021b5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T06:12:22Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-178a0955bea54001b9d1c978938021b52022-12-21T18:36:11ZengMDPI AGMolecules1420-30492019-03-01246115410.3390/molecules24061154molecules24061154Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of InflammasomeTing Liu0Qingxuan Zeng1Xiaoqiang Zhao2Wei Wei3Yinghong Li4Hongbin Deng5Danqing Song6Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaTwenty eight 7-substitued fangchinoline analogues, of which twenty two were novel, were synthesized and evaluated for their effect to inhibit lipopolysaccharide/nigericin (LPS/NIG)-induced IL-1β release at both cell and protein levels at the concentration of 5 μM. Among them, compound <b>6</b> exhibited promising inhibitory potency against IL-β activation with an IC<sub>50</sub> value of 3.7 μM. Preliminary mechanism study revealed that <b>6</b> might target NLRP3 protein, and then block ASC pyroptosome formation with-NLRP3, rather than acting on the activation of the NLRP3 inflammasome (NF-κB and MAPK pathways) or caspase-1 protein. Our current study supported the potential role of compound <b>6</b> against IL-β activation, and provided powerful information for developing fangchinoline derivatives into a novel class of anti-inflammatory agents.https://www.mdpi.com/1420-3049/24/6/1154fangchinolineAnti-inflammatoryIL-1βNLRP3 inflammasome |
| spellingShingle | Ting Liu Qingxuan Zeng Xiaoqiang Zhao Wei Wei Yinghong Li Hongbin Deng Danqing Song Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome Molecules fangchinoline Anti-inflammatory IL-1β NLRP3 inflammasome |
| title | Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome |
| title_full | Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome |
| title_fullStr | Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome |
| title_full_unstemmed | Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome |
| title_short | Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome |
| title_sort | synthesis and biological evaluation of fangchinoline derivatives as anti inflammatory agents through inactivation of inflammasome |
| topic | fangchinoline Anti-inflammatory IL-1β NLRP3 inflammasome |
| url | https://www.mdpi.com/1420-3049/24/6/1154 |
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