New flexible cembrane-type macrocyclic diterpenes as TNF-α inhibitors from the South China Sea soft coral Sarcophyton mililatensis

Qing Bu; Min Yang; Xian-Yun Yan; Li-Gong Yao; Yue-Wei Guo; Lin-Fu Liang

doi:10.1016/j.ijbiomac.2022.09.210

New flexible cembrane-type macrocyclic diterpenes as TNF-α inhibitors from the South China Sea soft coral Sarcophyton mililatensis

Int J Biol Macromol. 2022 Dec 1;222(Pt A):880-886. doi: 10.1016/j.ijbiomac.2022.09.210. Epub 2022 Sep 27.

Authors

Qing Bu¹, Min Yang², Xian-Yun Yan¹, Li-Gong Yao², Yue-Wei Guo³, Lin-Fu Liang⁴

Affiliations

¹ College of Materials Science and Engineering, Central South University of Forestry and Technology, 498 South Shaoshan Road, Changsha 410004, China.
² 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.
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; Shandong Laboratory of Yantai Drug Discovery, Bohai rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, 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; Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals and College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address: ywguo@simm.ac.cn.
⁴ College of Materials Science and Engineering, Central South University of Forestry and Technology, 498 South Shaoshan Road, Changsha 410004, China. Electronic address: lianglinfu@csuft.edu.cn.

PMID: 36179867
DOI: 10.1016/j.ijbiomac.2022.09.210

Abstract

A further study on the rarely reported soft coral Sarcophyton mililatensis disclosed five new flexible cembrane-type macrocyclic diterpenes sarcomililatols C-G (1-5) and two known analogues 6 and 7. The structures and absolute configurations of natural macrocyclic compounds 1-6 were established by the extensive spectroscopic analysis, X-ray diffraction analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT ECD) calculations, chemical reaction, and modified Mosher's method. In the bioassays, the macrocyclic diterpene 2 exhibited potent TNF-α inhibition (IC₅₀ = 6.1 μmol/L), which was better than the positive control dexamethasone (IC₅₀ = 8.7 μmol/L), and no obvious cytotoxicity against RAW264.7 cells with CC₅₀ values over 50 μmol/L, indicating natural macrocyclic compound 2 could be served as a model compound to develop a new and prospective chemotype of an anti-inflammatory lead compound or drug candidate.

Keywords: Absolute configuration; Cembrane; Macrocyclic diterpene; Sarcophyton mililatensis; TNF-α inhibitor.

MeSH terms

Animals
Anthozoa* / chemistry
China
Diterpenes* / chemistry
Diterpenes* / pharmacology
Molecular Structure
Prospective Studies
Tumor Necrosis Factor Inhibitors
Tumor Necrosis Factor-alpha

Substances

Tumor Necrosis Factor-alpha
Tumor Necrosis Factor Inhibitors
cembrane
Diterpenes