Three new cyclopiane-type diterpenes from a deep-sea derived fungus Penicillium sp. YPGA11 and their effects against human esophageal carcinoma cells

Cyclopianes, featuring a highly rigid 6/5/5/5-fused tetracyclic framework, are structurally unique and biologically significant and belong to a rarely reported diterpenoid family. Chemical investigation of an EtOAc extract of a deep-sea-derived Penicillium sp. led to the isolation of three new cyclopiane diterpenes, namely, conidiogenols C-D (1-2) and conidiogenone L (3). The structures were determined by extensive analyses of the spectroscopic data in association with ECD calculations and chemical conversion for configurational assignments. Compound 1 represents the second example of cyclopianes bearing a hydroxyl group at C-13. Compound 2, the third example of conidiogenols, possesses a distinct alpha-oriented 1-hydroxy group relative to other analogues. The bioassay study demonstrated that compounds 2 and 4-6 exhibited moderate inhibitory effects against five esophageal cancer cell lines with IC50 values ranging from 25 to 55 mu M. The cytotoxicities of all compounds toward esophageal cancer cell lines were evaluated for the first time.