A 3D screening approach identifies the compound epitajixanthone hydrate as a new inhibitor of cancer cell growth and invasion.

With unique advantages, the small-molecule anticancer drugs have recently gained growing attention. Particular strategies, exemplified by high-throughput screening, fragment-based drug discovery, virtual screening and knowledge-based design, have been developed to identify active compounds. However, such screens generally rely on sophisticated and expensive instrumentations. Herein, we developed a simple spheroids 3D culture system to enable direct screening of small molecules with reliable results. Using this system, we screened 27 fungal natural products and three fungal crude extracts for their inhibitory effects on cancer cell growth, and invasion. We identified that the compound M23 (epitajixanthone hydrate, a derivative of prenylxanthone) and the crude extracts (MPT-191) from the fungi Taxus chinensis showed potential anticancer activity. The effect of epitajixanthone hydrate on cancer cell growth and invasion were further confirmed by the assays of cells viability, trans-well migration and invasion, colony formation and cells reattachment. Overall, Epitajixanthone hydrate was identified as an effective inhibitor of cancer cell growth and invasion by our simple and fast screening platform.

Prenylated Indole Diterpene Alkaloids from a Mine-Soil-Derived Tolypocladium sp.

Ten new prenylated indole diterpene alkaloids, tolypocladin A-J (1-10), including four chlorinated metabolites, have been isolated from a culture of a mine-soil-derived fungus, Tolypocladium sp. XL115. The structures and absolute configurations of 1-10 were determined by spectroscopic analysis, ECD calculations, and comparison with known compounds. Compounds 1 and 8 displayed significant antimicrobial activities. In addition, compound 1 also showed weak cytotoxic activity against all tested human cancer cell lines and suppressed the growth and viability of the patient-derived HCC cells T1224.

Three new α-pyrone derivatives from the plant endophytic fungus Penicillium ochrochloronthe and their antibacterial, antifungal, and cytotoxic activities.

Three new 3,4,6-trisubstituted α-pyrone derivatives, namely 6-(2'R-hydroxy-3'E,5'E-diene-1'-heptyl)-4-hydroxy-3-methyl-2H-pyran-2-one (1), 6-(2'S-hydroxy-5'E-ene-1'-heptyl)-4-hydroxy-3-methyl-2H-pyran-2-one (2), and 6-(2'S-hydroxy-1'-heptyl)-4 -hydroxy-3-methyl-2H-pyran-2-one (3), together with one known compound trichodermic acid (4), were isolated from the solid-substrate fermentation culture of Penicillium ochrochloronthe associated the roots of Taxus media. Compounds 1-4 displayed the antimicrobial activity selectively against tested fungal and bacterial strains with minimum inhibitory concentration (MIC) values ranging from 12.5 to 100 µg/ml. Furthermore, we found that only compound 4 exhibited moderate cytotoxicity against five human cancer cells (A549, LN229, MGC, LOVO, and MDA231) with IC50 values of 51.45, 23.43, 39.16, 46.97, and 42.85 µg/ml, respectively.