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

• Published in: International journal of biological macromolecules Vol. 222; pp. 880 - 886
• Main Authors: Bu, Qing, Yang, Min, Yan, Xian-Yun, Yao, Li-Gong, Guo, Yue-Wei, Liang, Lin-Fu
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2022
• Subjects: Absolute configuration; Cembrane; Macrocyclic diterpene; Sarcophyton mililatensis; TNF-α inhibitor; Sarcophyton mililatensis; Cembrane; Macrocyclic diterpene; TNF-α inhibitor; Absolute configuration
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.09.210

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. [Display omitted] •Soft coral Sarcophyton mililatensis has been rarely studied.•Five new flexible cembrane-type macrocyclic diterpenes were obtained.•An array of approaches were employed to determine their absolute configurations.•Potent TNF-α inhibitory activity of the natural macrocyclic compounds was observed.