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

作者：Trmcic Milena V; Matovic Radomir V; Tovilovic Gordana I; Ristic Biljana Z; Trajkovic Vladimir S^*; Ferjancic Zorana B; Saicic Radomir N

来源：Organic and Biomolecular Chemistry, 2012, 10(25): 4933-4942.

DOI：10.1039/c2ob25514f

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.

• 出版日期2012