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.
Schobert
Rainer
R
Organic Chemistry Laboratory, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany. Rainer.Schobert@uni-bayreuth.de
Biersack
Bernhard
B
Knauer
Sebastian
S
Ocker
Matthias
M
D000363:Agaricales / Q000254:growth & development / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D002699:Chlorambucil / Q000737:chemistry / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000494:pharmacology; D004952:Esters / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
D003603:Cytotoxins; D003998:Dicarboxylic Acids; D004952:Esters; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C052673:illudin M; C100030:endothall; D002699:Chlorambucil; D004281:Docosahexaenoic Acids