Comazaphilones A-F, azaphilone derivatives from the marine sediment-derived fungus Penicillium commune QSD-17

Abstract

Chemical investigation of Penicillium commune QSD-17, a fungus isolated from a marine sediment sample collected in the southern China Sea, yielded six new azaphilone derivatives, namely, comazaphilones A-F (1-6). The structures of these compounds were established on the basis of spectroscopic analysis. Attempts to define the absolute configuration of these azaphilones through investigation of Mosher's esters failed, possibly due to steric crowding at C-6 and C-7 and due to the degradation of these azaphilone derivatives under the reaction conditions. The inhibitory activities of the six azaphilones against four bacteria, one pathogenic fungus, and seven tumor cell lines were evaluated. Compounds 3-5 displayed potent inhibitory activity against several of these bacteria, while compounds 4-6 showed cytotoxic activity against human pancreatic tumor cell line SW1990. The preliminary SAR results indicated that the double bond at C-10 and the location of the orsellinic acid unit at C-6 in these azaphilones are important for the antibacterial activity and cytotoxicity, respectively. This is the first report of the isolation of azaphilone derivatives from a marine sediment-derived fungus.