Identification of Cembrane Diterpenoids from Sinularia sp. That Reduce the Viability of Diffuse Pleural Mesothelioma Cell Lines

Diffuse pleural mesothelioma (DPM) is a rare but aggressive late-onset cancer. A high-throughput screen of a natural product fraction library identified fractions derived from an aqueous extract of Sinularia sp. soft coral that reduced the viability of DPM cell lines. Bioassay-guided fractionation of the parent extract resulted in the identification of 13 cembrane diterpenoids, including nine new natural products sinulariolones B–J (1–4, and 7–11), as the active principles. The planar structures of the new compounds were established by the analysis of NMR spectroscopic and MS spectrometric data. Their relative and absolute configurations were determined using a combined approach, including NOESY interpretation, modified Mosher’s method, ECD simulation, and single-crystal X-ray diffraction. All pure metabolites were tested for their effects on the viability of the DPM cell lines, and compounds 2, 3, 8, and 9 demonstrated low micromolar potency against these cancer cell lines.