Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel
| العنوان: | Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel |
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| المؤلفون: | Jose Viña, Vladimir V. Popik, Karunananda Bombuwala, Sonal Uppal, Thomas H. Kinstle, Carol A. Heckman, James B. Olesen |
| المصدر: | Beilstein Journal of Organic Chemistry, Vol 2, Iss 1, p 13 (2006) Beilstein Journal of Organic Chemistry |
| بيانات النشر: | Beilstein-Institut, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Organic Chemistry, Cell, Cancer, Promoter, Bioinformatics, medicine.disease, Full Research Paper, lcsh:QD241-441, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Paclitaxel, lcsh:Organic chemistry, Microtubule, Cancer cell, medicine, Cancer research, Colchicine, lcsh:Q, lcsh:Science, DNA |
| الوصف: | BackgroundTumor promoters enhance tumor yield in experimental animals without directly affecting the DNA of the cell. Promoters may play a role in the development of cancer, as humans are exposed to them in the environment. In work based on computer-assisted microscopy and sophisticated classification methods, we showed that cells could be classified by reference to a database of known normal and cancerous cell phenotypes. Promoters caused loss of properties specific to normal cells and gain of properties of cancer cells. Other compounds, including colchicine, had a similar effect. Colchicine given together with paclitaxel, however, caused cells to adopt properties of normal cells. This provided a rationale for tests of microtubule inhibitor combinations in cancer patients. The combination of a depolymerizing and a stabilizing agent is a superior anti-tumor treatment. The biological basis of the effect is not understood.ResultsA single compound containing both colchicine and paclitaxel structures was synthesized. Colchicine is an alkaloid with a trimethoxyphenyl ring (ring A), a ring with an acetamide linkage (ring B), and a tropolone ring (ring C). Although rings A and C are important for tubulin-binding activity, the acetamide linkage on ring B could be replaced by an amide containing a glutamate linker. Alteration of the C-7 site on paclitaxel similarly had little or no inhibitory effect on its biological activity. The linker was attached to this position. The coupled compound, colchitaxel (1), had some of the same effects on microtubules as the combination of starting compounds. It also caused shortening and fragmentation of the + end protein cap.ConclusionSince microtubule inhibitor combinations give results unlike those obtained with either inhibitor alone, it is important to determine how such combinations affect cell shape and growth. Colchitaxel shows a subset of the effects of the inhibitor combination. Thus, it may be able to bind the relevant cellular target of the combination. It will be useful to determine the basis of the shape reversal effect and possibly, the reasons for therapeutic efficacy of microtubule inhibitor combinations. |
| اللغة: | English |
| تدمد: | 1860-5397 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ebaa6c7e7250c62a9a3fe9ea1b1e542 https://doaj.org/article/32e97f442cec4b1abd7e7b39e1783d8f |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0ebaa6c7e7250c62a9a3fe9ea1b1e542 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18605397 |
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