Cembrane Diterpenes Possessing Nonaromatic Oxacycles from the Hainan Soft Coral Sarcophyton mililatensis

Documents on the chemical composition of the soft coral Sarcophyton mililatensis are sparse. The present investigation of the Hainan soft coral S. mililatensis resulted in the discovery of six new cembrane diterpenes, sarcoxacyclols A-F (1-6) and four known analogs (7-10). Their structures were elucidated by extensive spectroscopic analysis along with a comparison with the data in current literature. The nonaromatic oxacycles in their structures were the rarely found tetrahydrofuran ether across C-1 and C-12 and tetrahydropyran ether across C-1 and C-11, respectively. Moreover, the absolute configuration of compound 4 was established unambiguously by X-ray diffraction analysis using Ga K alpha radiation (lambda = 1.34139 angstrom). Based on the biogenetical consideration, the absolute configurations of other five new compounds were tentatively assumed. Assessment of the bioactivity for these secondary metabolites revealed that compound 1 exhibited significant tumor necrosis factor (TNF)-alpha inhibitory activity (IC50 = 9.5 mu mol/L), similar to the positive control dexamethasone (IC50 = 8.7 mu mol/L), but no obvious cytotoxicity towards RAW264.7 cells (CC50 > 50 mu mol/L). The preliminary molecular docking suggested the crucial roles of the hydroxyl and acetoxyl groups in the computational prediction of the binding mode between the diterpene and the protein.