Thiodiketopiperazines and Alkane Derivatives Produced by the Mangrove Sediment-Derived Fungus Penicillium ludwigii SCSIO 41408

A new trithiodiketopiperazine derivative, adametizine C (1), and five new alkane derivatives (7-11), were isolated from the mangrove sediment-derived fungus Penicillium ludwigii SCSIO 41408, together with five known dithiodiketopiperazine derivatives (2-6). Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configuration of 1 was determined by X-ray crystallographic analysis. In a variety of bioactivity screening, 1-5 exhibited some selective antifungal or antibacterial activities. Compounds 1-3 showed cytotoxicity against prostate cancer cell line 22Rv1 with half maximal inhibitory concentration (IC50) values of 13.0-13.9 mu M; moreover, 3 showed obvious activity against another prostate cancer PC-3 cells with an IC50 value of 5.1 mu M. Further experiments revealed that 3 could significantly reduce PC-3 cells colony formation and induce apoptosis in a dose-dependent manner. Several compounds also exhibited obvious inhibitory activities of lipopolysaccharide-induced nuclear factor-kappa B with IC50 values range from 8.2 to 21.5 mu M, and 1, 5, and 9 were further evaluated for their effects on receptor activator of NF-kappa B ligand (RANKL)-induced osteoclastogenesis. Adametizine C (1), with the strongest inhibitory activity against RANKL-induced osteoclast differentiation in bone marrow macrophage cells with 10 mu M, was suggested to be the promising lead compound for the treatment of osteoclast-related diseases.