Diversity-oriented synthesis of cembranoid derivatives as potential anti-inflammatory agents

Cong Zhang; Heng Li; Jin Liu; Moting Liu; Hao Zhang; Kai-Xian Chen; Yue-Wei Guo; Wei Tang; Xu-Wen Li

doi:10.1016/j.bioorg.2021.104887

Diversity-oriented synthesis of cembranoid derivatives as potential anti-inflammatory agents

Bioorg Chem. 2021 Jun:111:104887. doi: 10.1016/j.bioorg.2021.104887. Epub 2021 Apr 6.

Authors

Cong Zhang¹, Heng Li², Jin Liu³, Moting Liu², Hao Zhang³, Kai-Xian Chen⁴, Yue-Wei Guo⁴, Wei Tang⁵, Xu-Wen Li⁶

Affiliations

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China; Nano Science and Technology Institute, University of Science and Technology of China, 166 Ren Ai Road, Suzhou 215123, China.
² Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
⁴ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China; Open Studio for Druggability Research of Marine Natural Products, Pilot National Laboratory for Marine Science and Technology (Qingdao), 1 Wenhai Road, Aoshanwei, Jimo, Qingdao, 266237, China.
⁵ Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: tangwei@simm.ac.cn.
⁶ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China; Open Studio for Druggability Research of Marine Natural Products, Pilot National Laboratory for Marine Science and Technology (Qingdao), 1 Wenhai Road, Aoshanwei, Jimo, Qingdao, 266237, China. Electronic address: xwli@simm.ac.cn.

PMID: 33865055
DOI: 10.1016/j.bioorg.2021.104887

Abstract

Eleven novel cembranoid derivatives were designed, synthesized, and evaluated for their inflammation related activities on the basis of our isolated and previously reported anti-inflammatory marine cembranoids. In bioassay, compound 11 displayed the most promising inhibitory effects with IC₅₀ value of 1.1 μM for the TNF-α inhibitory activity. The further mechanism study of 11 on the inflammatory signaling transduction of RAW264.7 cells was also performed. This research may give an insight for the discovery of marine cembranoid derived anti-inflammatory drug leads.

Keywords: Anti-inflammation; Cembranoid; Marine natural product; Structure Activity Relationship; molecular docking; structuremodification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / pharmacology*
Cells, Cultured
Diterpenes / chemical synthesis
Diterpenes / chemistry
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Mice
Models, Molecular
Molecular Structure
RAW 264.7 Cells
Signal Transduction / drug effects
Structure-Activity Relationship
Transforming Growth Factor beta / antagonists & inhibitors*

Substances

Anti-Inflammatory Agents
Diterpenes
Transforming Growth Factor beta
cembrane