Čeština
EnglishPaclitaxel conjugation with the analog of the gonadotropin-releasing hormone as a targeting moiety
Přibylová M., Dvořáková M., Hanušová V., Nemethová I., Skálová L., Vaněk T.
INTERNATIONAL JOURNAL OF PHARMACEUTICS 415[1-2]: 175-180, 2011
Keywords: Paclitaxel; GnRH; Targeted drug delivery; Cancer
Abstract: 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. In conclusion, the paclitaxel conjugate with the analog of GnRH exhibited targeted antiproliferative effect for which its further testing will be implemented.
DOI:
Fulltext: contact IEB authors
IEB authors: Marcela Dvořáková, Marie Kvasnicová, Tomáš Vaněk
INTERNATIONAL JOURNAL OF PHARMACEUTICS 415[1-2]: 175-180, 2011
Keywords: Paclitaxel; GnRH; Targeted drug delivery; Cancer
Abstract: 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. In conclusion, the paclitaxel conjugate with the analog of GnRH exhibited targeted antiproliferative effect for which its further testing will be implemented.
DOI:
Fulltext: contact IEB authors
IEB authors: Marcela Dvořáková, Marie Kvasnicová, Tomáš Vaněk