Gliotoxin Analogues from a Marine-Derived Fungus, Penicillium sp., and Their Cytotoxic and Histone Methyltransferase Inhibitory Activities

Seven gliotoxin-related compounds were isolated from the fungus Penicillium sp. strain JMF034, obtained from deep sea sediments of Suruga Bay, Japan. These included two new metabolites, bis­(dethio)-10a-methylthio-3a-deoxy-3,3a-didehydrogliotoxin (1) and 6-deoxy-5a,6-didehydrogliotoxin (2), and five known metabolites (3–7). The structures of the new compounds were elucidated by analysis of spectroscopic data and the application of the modified Mosher’s analysis. All of the compounds exhibited cytotoxic activity, whereas compounds containing a disulfide bond showed potent inhibitory activity against histone methyltransferase (HMT) G9a. None of them inhibited HMT SET7/9.