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Spiro-bicyclo[2.2.2]octane derivatives as paclitaxel mimetics. Synthesis and toxicity evaluation in breast cancer cell lines.

Manner, Sophie LU ; Oltner, Viveca; Oredsson, Stina LU ; Ellervik, Ulf LU and Frejd, Torbjörn LU (2013) In Organic and Biomolecular Chemistry 11(41). p.7134-7144
Abstract
Paclitaxel is one of the most important anti-cancer agents introduced during the last 20 years. However, the use of paclitaxel is limited by undesirable side effects as well as the development of drug resistance. Here, we report a synthetic strategy towards spiro-bicyclo[2.2.2]octane derivatives, which includes double Michael addition and ring-closing metathesis as key synthetic steps. This strategy was used to synthesize a series of spiro-bicyclic compounds designed to be paclitaxel mimetics, which were evaluated in human breast-derived cell lines. One of these paclitaxel mimetics showed toxicity, although at higher concentrations than paclitaxel itself. In addition, two other spiro-bicyclic compounds, lacking the paclitaxel side chain,... (More)
Paclitaxel is one of the most important anti-cancer agents introduced during the last 20 years. However, the use of paclitaxel is limited by undesirable side effects as well as the development of drug resistance. Here, we report a synthetic strategy towards spiro-bicyclo[2.2.2]octane derivatives, which includes double Michael addition and ring-closing metathesis as key synthetic steps. This strategy was used to synthesize a series of spiro-bicyclic compounds designed to be paclitaxel mimetics, which were evaluated in human breast-derived cell lines. One of these paclitaxel mimetics showed toxicity, although at higher concentrations than paclitaxel itself. In addition, two other spiro-bicyclic compounds, lacking the paclitaxel side chain, showed toxicity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Organic and Biomolecular Chemistry
volume
11
issue
41
pages
7134 - 7144
publisher
Royal Society of Chemistry
external identifiers
  • wos:000326010300015
  • pmid:24057031
  • scopus:84885087746
ISSN
1477-0539
DOI
10.1039/c3ob41417e
language
English
LU publication?
yes
id
15e2d3f7-0371-43b8-ad1c-78b531e99a7d (old id 4065510)
date added to LUP
2013-11-13 17:28:43
date last changed
2019-02-20 03:16:14
@article{15e2d3f7-0371-43b8-ad1c-78b531e99a7d,
  abstract     = {Paclitaxel is one of the most important anti-cancer agents introduced during the last 20 years. However, the use of paclitaxel is limited by undesirable side effects as well as the development of drug resistance. Here, we report a synthetic strategy towards spiro-bicyclo[2.2.2]octane derivatives, which includes double Michael addition and ring-closing metathesis as key synthetic steps. This strategy was used to synthesize a series of spiro-bicyclic compounds designed to be paclitaxel mimetics, which were evaluated in human breast-derived cell lines. One of these paclitaxel mimetics showed toxicity, although at higher concentrations than paclitaxel itself. In addition, two other spiro-bicyclic compounds, lacking the paclitaxel side chain, showed toxicity.},
  author       = {Manner, Sophie and Oltner, Viveca and Oredsson, Stina and Ellervik, Ulf and Frejd, Torbjörn},
  issn         = {1477-0539},
  language     = {eng},
  number       = {41},
  pages        = {7134--7144},
  publisher    = {Royal Society of Chemistry},
  series       = {Organic and Biomolecular Chemistry},
  title        = {Spiro-bicyclo[2.2.2]octane derivatives as paclitaxel mimetics. Synthesis and toxicity evaluation in breast cancer cell lines.},
  url          = {http://dx.doi.org/10.1039/c3ob41417e},
  volume       = {11},
  year         = {2013},
}