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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, compound 6 exhibited pr...

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Detalles Bibliográficos
Autores principales: Liu, Ting, Zeng, Qingxuan, Zhao, Xiaoqiang, Wei, Wei, Li, Yinghong, Deng, Hongbin, Song, Danqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470529/
https://www.ncbi.nlm.nih.gov/pubmed/30909541
http://dx.doi.org/10.3390/molecules24061154
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author Liu, Ting
Zeng, Qingxuan
Zhao, Xiaoqiang
Wei, Wei
Li, Yinghong
Deng, Hongbin
Song, Danqing
author_facet Liu, Ting
Zeng, Qingxuan
Zhao, Xiaoqiang
Wei, Wei
Li, Yinghong
Deng, Hongbin
Song, Danqing
author_sort Liu, Ting
collection PubMed
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 6 exhibited promising inhibitory potency against IL-β activation with an IC(50) value of 3.7 μM. Preliminary mechanism study revealed that 6 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 6 against IL-β activation, and provided powerful information for developing fangchinoline derivatives into a novel class of anti-inflammatory agents.
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spelling pubmed-64705292019-04-26 Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome Liu, Ting Zeng, Qingxuan Zhao, Xiaoqiang Wei, Wei Li, Yinghong Deng, Hongbin Song, Danqing Molecules Article 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 6 exhibited promising inhibitory potency against IL-β activation with an IC(50) value of 3.7 μM. Preliminary mechanism study revealed that 6 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 6 against IL-β activation, and provided powerful information for developing fangchinoline derivatives into a novel class of anti-inflammatory agents. MDPI 2019-03-23 /pmc/articles/PMC6470529/ /pubmed/30909541 http://dx.doi.org/10.3390/molecules24061154 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Ting
Zeng, Qingxuan
Zhao, Xiaoqiang
Wei, Wei
Li, Yinghong
Deng, Hongbin
Song, Danqing
Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of 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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470529/
https://www.ncbi.nlm.nih.gov/pubmed/30909541
http://dx.doi.org/10.3390/molecules24061154
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