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Issue 25, 2012
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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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Abstract

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 G2/M cell cycle arrest-dependent apoptosis.

Graphical abstract: 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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Article information


Submitted
09 Mar 2012
Accepted
02 May 2012
First published
02 May 2012

Org. Biomol. Chem., 2012,10, 4933-4942
Article type
Paper

A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids

M. V. Trmcic, R. V. Matovic, G. I. Tovilovic, B. Z. Ristic, V. S. Trajkovic, Z. B. Ferjancic and R. N. Saicic, Org. Biomol. Chem., 2012, 10, 4933
DOI: 10.1039/C2OB25514F

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