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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Agaricales / growth & development
-
Agaricales / metabolism*
-
Cell Line, Tumor / drug effects
-
Chlorambucil / chemistry
-
Chlorambucil / pharmacology
-
Colonic Neoplasms / metabolism
-
Colonic Neoplasms / pathology
-
Cytotoxins / chemistry
-
Cytotoxins / isolation & purification
-
Cytotoxins / pharmacology*
-
Dicarboxylic Acids / chemistry
-
Dicarboxylic Acids / pharmacology
-
Docosahexaenoic Acids / chemistry
-
Docosahexaenoic Acids / pharmacology
-
Esters / chemistry
-
Esters / pharmacology*
-
Fibroblasts / cytology
-
Fibroblasts / drug effects*
-
Humans
-
Pancreatic Neoplasms / metabolism
-
Pancreatic Neoplasms / pathology
-
Polycyclic Sesquiterpenes
-
Sesquiterpenes / chemistry
-
Sesquiterpenes / isolation & purification
-
Sesquiterpenes / pharmacology
-
Structure-Activity Relationship
-
Toxicity Tests
Substances
-
Cytotoxins
-
Dicarboxylic Acids
-
Esters
-
Polycyclic Sesquiterpenes
-
Sesquiterpenes
-
illudin M
-
endothall
-
Chlorambucil
-
Docosahexaenoic Acids