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

ABSTRACT: 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-1? release at both cell and protein levels at the concentration of 5 ?M. Among them, compound 6 exhibited promising inhibitory potency against IL-? activation with an IC50 value of 3.7 ?M. 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-?B and MAPK pathways) or caspase-1 protein. Our current study supported the potential role of compound 6 against IL-? activation, and provided powerful information for developing fangchinoline derivatives into a novel class of anti-inflammatory agents.

SUBMITTER: Liu T

PROVIDER: S-EPMC6470529 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Liu Ting T Zeng Qingxuan Q Zhao Xiaoqiang X Wei Wei W Li Yinghong Y Deng Hongbin H Song Danqing D

Molecules (Basel, Switzerland) 20190323 6

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 IC50 value of 3.7 μM. Preliminary mechanism study revealed that 6 might target NLRP3 protein, and then block ASC pyr ...[more]

PMID: 30909541

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