Conjugates of the fungal cytotoxin illudin M with improved tumour specificity

  • Bioorg Med Chem. 2008 Sep 15;16(18):8592-7. doi: 10.1016/j.bmc.2008.08.015.
Rainer Schobert  1 ,  Bernhard Biersack ,  Sebastian Knauer ,  Matthias Ocker
Affiliations
  • 1. Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany. [email protected]
PMID: 18715789 DOI: 10.1016/j.bmc.2008.08.015
Abstract

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.

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