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Witold S. Cieśliński 1Ryszard Kinas 1Marta Świtalska 2Joanna Wietrzyk Wojciech Mól 3Stanisław Boryczka 3

1. Research Laboratory AGROPHARM SA, Starościńska 28, Tuszyn 98-420, Poland
2. Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland
3. Medical University of Silesia, Department of Organic Chemistry, Jagiellonska 4, Sosnowiec 41-200, Poland


Paclitaxel is one of the most important chemotherapeutic agent for clinical treatment of ovarian and breast cancer. Due to its high cytotoxic activity and unique mechanism of action, and also because of its drawbacks (poor water solubility and iduction of multi-drug resistance), paclitaxel has become the subject of extensive structure-activity relationship studies, in order to obtain better insight into its mechanism of action at the molecular level and to prepare new, more active analogues with better pharmacological properties. Many derivatives of paclitaxel have been reported to data, some of which have been found to be more, and some less potent than paclitaxel.

Here we wish to report the synthesis of paclitaxel derivative with propargyl group at C-10 as an example of alkynyl pharmacophore which may significantly modify the chemical, physical and biological properties of such substances. Compouns 5 was prepared in 4 steps starting from 10-deacetylbaccatin III (10-DAB-III) (1) isolated from natural resources (needles of Taxus baccata). Silylation and next propargylation of 1 gave 7-TES-10-PRODAB-III (3). Compound 3 was condensated with protected taxol side chain, using DCC as a condensing agent. Hydrolysis of the product of condensation 4 provided 10-propargyldeacetylpaclitaxel (5).


The obtained compounds were tested for their antiproliferative activity in vitro against the cells of human lung carcinoma A549, human breast carcinoma MCF-7 and mice melanoma B16-F0. The compound 5 was active only against MCF-7 and 3 was active against all tested cell lines. However, all compounds were about 100-1000 fold less active than paclitaxel.


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Related papers

Presentation: Poster at V Multidyscyplinarna Konferencja Nauki o Leku, by Witold S. Cieśliński
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2006-02-02 11:38
Revised:   2009-06-07 00:44