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. 2011, 415(1-2), 175-180. ISSN 0378-5173. E-ISSN 1873-3476

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.