RESUMEN

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.

Asunto(s)

Autofagia/efectos de los fármacos , Paclitaxel/química , Espironolactona/análogos & derivados , Línea Celular Tumoral , Humanos , Estructura Molecular , Paclitaxel/farmacología