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

摘要

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 GI50 values ranging from 0.14 to 2.01 μM.