A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids
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AuthorsTrmcic, Milena V.
Tovilovic, Gordana I.
Ristic, Biljana Z.
Trajkovic, Vladimir S.
Saičić, Radomir N.
Article (Published version)
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The design, synthesis and biological evaluation of a novel C, D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.
Source:Organic & Biomolecular Chemistry, 2012, 10, 25, 4933-4942
- Royal Soc Chemistry, Cambridge