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

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.