Paclitaxel conjugation with the analog of the gonadotropin-releasing hormone as a targeting moiety

0370667 - ÚEB 2012 RIV GB eng J - Článek v odborném periodiku
Přibylová, Marie - Dvořáková, Marcela - Hanusová, V. - Nemethová, I. - Skálová, L. - Vaněk, Tomáš
Paclitaxel conjugation with the analog of the gonadotropin-releasing hormone as a targeting moiety.
International Journal of Pharmaceutics. Roč. 415, 1-2 (2011), s. 175-180. ISSN 0378-5173. E-ISSN 1873-3476
Grant CEP: GA MŠMT ME08070
Výzkumný záměr: CEZ:AV0Z50380511
Klíčová slova: Paclitaxel * GnRH * Targeted drug delivery
Kód oboru RIV: EI - Biotechnologie a bionika
Impakt faktor: 3.350, rok: 2011

A new targeted conjugates in which paclitaxel was used as a cytostatic compound and an analog of the gonadotropin-releasing hormone (GnRH) as a targeting moiety were synthesized. The molecule of the peptide hormone GnRH was modified to allow its connection to paclitaxel via spacer. The conjugates were prepared as prodrugs using 2'-hydroxyl group of paclitaxel. 4-Maleimidobutyric acid and chloroacetic acid served as spacers. The structures of the prepared derivatives were analysed by NMR and HR-MS. The conjugates MP264 and MP265 were chosen and their antiproliferative effect was tested in the breast cancer cell line MCF-7 using the MTT test of cell viability and neutral red uptake test. In MCF-7 cells, conjugate MP265 showed higher antiproliferative effect than paclitaxel alone. Receptor saturation tests showed that the unconjugated peptide analog of GnRH decreased efficacy of conjugate MP265 in concentration- and time-dependent manner.
Trvalý link: http://hdl.handle.net/11104/0204395