Antitumor Chemical Constituents Of The Deep-Sea-Derived Penicillium Mali And Hypocrea Sp.

Utilizing the OSMAC strategy,two deep-sea-derived fungi with antitumor bioactivity and a broad spectrum of components were selected for systematically chemical investigation.From the Penicillium mali MCCC 3A00140,50 compounds were obtained including eight heptylcyclohexanes（1,2,5-10）,nine polyketones（3,4,11,18,35,39,44-46）,nine acids or acid esters（12-17,38,43,48）,three cyclohexanediones（19-20,50）,five compactin derivatives（21-25）,three peptides（26,36-37）,eight alkaloids（27-34）,two steroids（40-41）,one aliphatic acid derivatives（42）,one phenol（48）,and one meroterpenoids（49）.There are eight new compounds among them,which are 1-5,7-8 and 11.From the deep-sea-derived Hypocrea sp.ZEN14（corn medium）,36 components were purified and identified,containing nine alkaloids or nitrogenous compounds（51-55,78-80,82）,two terpenes（56-57）,six steroids（58-53）,eight polyketones（64-69,83-84）,nine phenols or acids（70-77,81）,and two amino acid derivatives（85-86）.Compounds 51 and 52 are novel single S-bridge ETPs.Compound 58 is an unique steroid similar to the known compounds withanolides.However,from the Hypocrea sp.ZEN14（rice medium）,a series of polyketones（87-90）were isolated,especially aflatoxins.A number of above secondary metabolites were assessed for several antitumor bioactive measurement.Compound 1 exhibited significant cytotoxicity against PC3-KLF5/KQ cell line(IC₅₀=10μM).Compounds 51 and 52 displayed different extent effects cytotoxicity against a series of tumor cell lines.Compound 51 showed remarkable cytotoxicity against U2OS and 786-O cell lines(IC₅₀=0.2μM).Otherwise,compounds 51 and 52 represent selective cytotoxicity against MDA-MB-231,U937,Hela,MCF-7 cell lines(IC₅₀ values of 0.5–20μM).In conclusion,90 compounds were isolated from two dee-sea-derived fungi using antitumor bioactivity as guidance,including 11 new compounds.Among new compounds,three exhibited significant antitumor effect.It provides antitumor lead compounds for the development of marine drugs.