Cytotoxic Illudane Sesquiterpenes from the Fungus Granulobasidium vellereum (Ellis and Cragin) Jülich.

ABSTRACT

Eight illudane sesquiterpenes were obtained from the wood-decomposing fungus Granulobasidium vellereum (Ellis and Cragin) Jülich; among them were the enantiomers of the known compounds illudin M (1) and dihydroilludin M (4) and the diastereomers of illudin M (2) and illudin S (3), as well as two previously undescribed illudanes (5, 6). The cytotoxicity of compounds 1-4 and 6 was evaluated against two tumor cell lines (Huh7 and MT4), which showed that compounds 1-3 had potent cytotoxic activity, whereas compounds 4 and 6 had no or only moderate effects at concentrations up to 400 µM. Surprisingly, both compounds 2 and 3 were about 10 times more potent than 1. When the chemical reactivity of 1 and 2 was tested, compound 2 was shown to have a substantially higher reaction rate when reacted both with 2 M HCl and with cysteine, indicating that the difference in cytotoxicity is probably due to chemical reactivity and not to enzymatic affinity.