Synthesis and biological properties of C12,13-cyclopropyl-epothilone A and related epothilones.
Chem Biol
; 5(7): 365-72, 1998 Jul.
Article
em En
| MEDLINE
| ID: mdl-9662505
ABSTRACT
BACKGROUND:
The epothilones are natural substances that are potently cytotoxic, having an almost identical mode of action to Taxoltrade mark as tubulin-polymerization and microtubule-stabilizing agents. The development of detailed structure-activity relationships for these compounds and the further elucidation of their mechanism of action is of high priority.RESULTS:
The chemical synthesis of the C12,13-cyclopropyl analog of epothilone A and its C12,13-trans-diastereoisomer has been accomplished. These compounds and several other epothilone analogs have been screened for their ability to induce tubulin polymerization and death of a number of tumor cells. Several interesting structure-activity trends within this family of compounds were identified.CONCLUSIONS:
The results of the biological tests conducted in this study have demonstrated that, although a number of positions on the epothilone skeleton are amenable to modification without significant loss of biological activity, the replacement of the epoxide moiety of epothilone A with a cyclopropyl group leads to total loss of activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Epotilonas
/
Lactonas
/
Antineoplásicos
Limite:
Animals
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article