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...

Full description

Bibliographic Details
Main Authors:	Ting Liu, Qingxuan Zeng, Xiaoqiang Zhao, Wei Wei, Yinghong Li, Hongbin Deng, Danqing Song
Format:	Article
Language:	English
Published:	MDPI AG 2019-03-01
Series:	Molecules
Subjects:	fangchinoline Anti-inflammatory IL-1β NLRP3 inflammasome
Online Access:	https://www.mdpi.com/1420-3049/24/6/1154

id	doaj-178a0955bea54001b9d1c978938021b5
record_format	Article
spelling	doaj-178a0955bea54001b9d1c978938021b52020-11-24T20:41:56ZengMDPI 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
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Ting Liu Qingxuan Zeng Xiaoqiang Zhao Wei Wei Yinghong Li Hongbin Deng Danqing Song
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
author_facet	Ting Liu Qingxuan Zeng Xiaoqiang Zhao Wei Wei Yinghong Li Hongbin Deng Danqing Song
author_sort	Ting Liu
title	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_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_sort	synthesis and biological evaluation of fangchinoline derivatives as anti-inflammatory agents through inactivation of inflammasome
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2019-03-01
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.
topic	fangchinoline Anti-inflammatory IL-1β NLRP3 inflammasome
url	https://www.mdpi.com/1420-3049/24/6/1154
work_keys_str_mv	AT tingliu synthesisandbiologicalevaluationoffangchinolinederivativesasantiinflammatoryagentsthroughinactivationofinflammasome AT qingxuanzeng synthesisandbiologicalevaluationoffangchinolinederivativesasantiinflammatoryagentsthroughinactivationofinflammasome AT xiaoqiangzhao synthesisandbiologicalevaluationoffangchinolinederivativesasantiinflammatoryagentsthroughinactivationofinflammasome AT weiwei synthesisandbiologicalevaluationoffangchinolinederivativesasantiinflammatoryagentsthroughinactivationofinflammasome AT yinghongli synthesisandbiologicalevaluationoffangchinolinederivativesasantiinflammatoryagentsthroughinactivationofinflammasome AT hongbindeng synthesisandbiologicalevaluationoffangchinolinederivativesasantiinflammatoryagentsthroughinactivationofinflammasome AT danqingsong synthesisandbiologicalevaluationoffangchinolinederivativesasantiinflammatoryagentsthroughinactivationofinflammasome
_version_	1716823847783628800

Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome

Similar Items