SMART-Guided Isolation and Identification of Seven-Membered Cembranolides with Anti-Inflammation Activity from the Soft Coral Sinularia mollis.

The first systematic chemical investigation on Sinularia mollis resulted in the isolation and identification of 36 seven-membered cembranolides, including 14 new compounds named sinumollolides A-N (1-14) and 22 known analogs (15-36) by HSQC-based small molecule accurate recognition technology (SMART). Their structures were characterized by spectroscopic methods (1D/2D NMR and UV), HRESIMS, quantum chemical calculations (DP4+ analysis and ECD calculations), and X-ray diffraction analysis. In zebrafish assays, compounds 1, 2, 4, and 5 exhibited anti-inflammatory activity at 20 μM by inhibiting the number of macrophages around the neuromasts, with inhibition rates ranging from 30.4% to 45.6%. Moreover, the two most bioactive and less toxic compounds, 1 and 5, featuring a 14-membered macrocyclic lactone scaffold with several hydroxyl groups and a seven-membered α, β-unsaturated lactone moiety, can inhibit inflammation by suppressing the secretion of inflammatory cytokines at 10 μM in LPS-stimulated BV-2 cells.