2. Academic Validation
  3. Design, synthesis and biological evaluation of tanshinone IIA derivatives as NLRP3 inflammasome inhibitors

Design, synthesis and biological evaluation of tanshinone IIA derivatives as NLRP3 inflammasome inhibitors

  • Bioorg Med Chem Lett. 2024 May 15:104:129725. doi: 10.1016/j.bmcl.2024.129725.
Hao Chen 1,  Hu Yue 1,  Yuyun Yan 1,  Nannan Wu 2,  Dan Wu 1,  Ping Sun 3,  Wenhui Hu 4,  Zhongjin Yang 5
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Target, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
  • 2 Department of Pharmacy, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524045, China.
  • 3 Key Laboratory of Molecular Target, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China. Electronic address: sun_ping@gzhmu.edu.cn.
  • 4 Key Laboratory of Molecular Target, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China. Electronic address: huwenhui@gzhmu.edu.cn.
  • 5 Key Laboratory of Molecular Target, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China. Electronic address: yzj23@gzhmu.edu.cn.
PMID: 38555073 DOI: 10.1016/j.bmcl.2024.129725
Abstract

Natural product structures have long provided valuable pharmacophores and even candidates for drug discovery. Tanshinone scaffold showed moderately inhibitory activity in NLRP3 inflammasome/IL-1β pathway. Herein, we designed a series of derivatives on different regions of Tanshinone IIA (TNA) scaffold. The biological evaluation identified compound T10, a scaffold hybrid of TNA and salicylic acid, as a potent NLRP3 inflammasome inhibitor. Mechanistically, T10 inhibits the production of ROS and prevents NLRP3 inflammasome-dependent IL-1β production. In addition, treatment with T10 significantly attenuated inflammatory response in DSS-induced peritonitis. Our work describes a potential tanshinone-based derivative, which needs to be further structurally optimized as NLRP3 inflammasome inhibitors for treating inflammatory disorders.

Keywords

IL-1β; NLRP3 inflammasome; Peritonitis; Tanshinone.

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