Conjugates of the fungal cytotoxin illudin M with improved tumour specificity

A simplified procedure for the isolation of gram quantities of illudin M from culture broths of basidiomycete Omphalotus olearius is described. Esters of illudin M with docosahexaenoic acid, chlorambucil, demethylcantharidinic acid (endothall) and 2,2′-bipyridyl-5,5′-dicarboxylic acid were synthesised and tested for cytotoxicity and induction of apoptosis in two clinically relevant tumour cell lines (Panc-1 pancreas carcinoma and HT-29 colon carcinoma) and in non-malignant human foreskin fibroblasts. The demethylcantharidin and the bipyridine conjugates retained the cytotoxicity of the parent illudin M while displaying an improved specificity for the tumour cells over the fibroblasts.

Compared with illudin M, its esters with demethylcantharidinic acid (endothall) and 2,2′-bipyridyl-5,5′-dicarboxylic acid retained the high cytotoxicity while displaying an improved specificity for cells of Panc-1 pancreas and HT-29 colon carcinomas over non-malignant human fibroblasts.Figure optionsDownload as PowerPoint slide