New Ophiobolin Derivatives from the Marine Fungus Aspergillus flocculosus and Their Cytotoxicities against Cancer Cells

Five new sesterterpenes, 14,15-dehydro-6-epi-ophiobolin K (1), 14,15-dehydro- ophiobolin K (2), 14,15-dehydro-6-epi-ophiobolin G (3), 14,15-dehydro-ophiobolin G (4) and 14,15-dehydro-(Z)-14-ophiobolin G (5), together with four known ophiobolins (6-9) were isolated from the marine fungus Aspergillus flocculosus derived from the seaweed Padina sp. collected in Vietnam. The five new ophiobolins were first isolated as ophiobolin derivatives consisting of a fully unsaturated side chain. Their structures were elucidated via spectroscopic methods including 1D, 2D NMR and HR-ESIMS. The absolute configurations were determined by the comparison of chemical shifts and optical rotation values with those of known ophiobolins. All compounds (1-9) were then evaluated for their cytotoxicity against six cancer cell lines, HCT-15, NUGC-3, NCI-H23, ACHN, PC-3 and MDA-MB-231. All the compounds showed potent cytotoxicity with GI(50) values ranging from 0.14 to 2.01 mu M.