Geumsanols, Highly Oxygenated Azaphilones Produced by Penicillium sp. 11A109 from a Ginseng Field

Structurally diverse fungal metabolites have played important roles as chemical probes that help to understand biology. Chemical biology using diverse fungal metabolites has been developed with explosive developments of biological methodology and it is required to access a variety of fungal strains and their secondary metabolites for in depth research. In this respect we have investigated fungi from ecologically diverse environments in Korea and their secondary metabolites by fraction library and analysis of HPLC-PDA profiles. In the course of our successive efforts to isolate structurally diverse fungal metabolites, chemical investigation of one fungal strain Penicillium sp. 11A109 from soil samples of Geumsan in Korea aroused our interest because it produced a number of derivatives showing the characteristic UV absorbance spectra. As a result, seven new azaphilones geumsanol A-G and the six known analogues, WB, isochromophilone VI, sclerotioramine, 2,4-Dihydroxy-6-(5,7-dimethyl-2-oxo-3,5-nonadienyl)-3-methylbenzaldehyde, acetyldechloroisochromophilone III, and sclerotiorin were isolated. The structures of thirteen azaphilones were assigned on the basis of spectroscopic data and ESIMS analysis. New azaphilones possess acyclic 1,2-diol moiety as a common structural feature. The relative and absolute configurations of new compounds were determined by interpretation of NOESY, HETLOC, CD spectra and chemical derivatization methods including Mosher’s analysis and acetonide formation. New azaphilones were tested for cytotoxic activities against Hep3B, MDA-MB-231, K562, HL-60, Jurkat and P388 cell lines. Only geumsanol A showed weak cytotoxic activity against the murine P388 lymphocytic leukemia cell line.

Keywords : Secondary metabolites, Azaphilones