Abstract
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.