In vitro cytotoxicity of melleolide antibiotics: structural and mechanistic aspects.

Melleolide sesquiterpene aryl esters are secondary products of the mushroom genus Armillaria. We compared the cytotoxicity of eleven melleolides--five thereof are new natural products--against four human cancer cell lines. Armillaridin, 4-O-methylarmillaridin, and dehydroarmillylorsellinate were most active, at IC(50) = 3.0, 4.1 and 5.0 μM, respectively, against Jurkat T cells for the former two compounds, and K-562 cells for the latter. Dehydroarmillylorsellinate did not inhibit respiration and RNA-synthesis of K-562 cells at 5 μM. However, replication of DNA dropped to 35% after 120 min at this concentration, and translational activity also decreased.