Synthesis and antitumor activity of peptide-paclitaxel conjugates.
J Pept Sci
; 13(10): 662-71, 2007 Oct.
Article
en En
| MEDLINE
| ID: mdl-17787026
Paclitaxel (Pac) is the most important anticancer drug used mainly in treatment of breast, lung, and ovarian cancer and is being investigated for use as a single agent for treatment of lung cancer, advanced head and neck cancers, and adenocarcinomas of the upper gastrointestinal tract. In this work, we present the synthesis of five 2'-paclitaxel-substituted analogs in which paclitaxel was covalently bound to peptides or as multiple copies to synthetic carriers. Ac-Cys(CH(2)CO-2'-Pac)-Arg-Gly-Asp-Arg-NH(2), Folyl-Cys(CH(2)CO-2'-Pac)-Arg-Gly-Asp-Ser-NH(2), Ac-[Lys-Aib-Cys(CH(2)CO-2'-Pac)](2)-NH(2), Ac-[Lys-Aib-Cys(CH(2)CO-2'-Pac)](3)-NH(2) and Ac-[Lys-Aib-Cys(CH(2)CO-2'-Pac)](4)-NH(2) were synthesized using 2'-halogeno-acetylated paclitaxel derivatives. Paclitaxel conjugates showed greater solubility in water than paclitaxel and inhibited the proliferation of human breast, prostate, and cervical cancer cell lines. Although all synthesized compounds had an antiproliferative activity, the Ac-[Lys-Aib-Cys(CH(2)CO-2'-Pac)](4)-NH(2) derivative showed improved biological activity in comparison with paclitaxel in cervical and prostate human cancer cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Paclitaxel
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
J Pept Sci
Asunto de la revista:
BIOQUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Grecia
Pais de publicación:
Reino Unido