Paclitaxel, docetaxel and a series of new analogs synthesized from 14-hydroxy-10-deacetylbaccatin III (14-OH-DAB), a natural diterpene closely related to the core synthon of the 2 above prototypes, were tested in vitro for their growth-inhibitory activity on different human cancer cell lines, including some expressing the classic multidrugresistant (MDR) phenotype (MCF-7 ADRr and CEM VBLr). The 14-OH-DAB derivatives showed enhanced anti-proliferative activity as compared to the parent compounds on the MDR-positive cancer cell lines. Particularly, IDN 5109 showed a 25-to 30-fold higher activity than paclitaxel. The fold change in activity between paclitaxel and analogs (IC 50 paclitaxel/IC 50 analogs) on the MDR-positive cell lines was calculated and a significant correlation observed. As far as the MDR-negative MDA-MB 231 cells are concerned, docetaxel and IDN 5109 exhibited a more potent activity than paclitaxel. On the basis of the data obtained on cell growth inhibition, we selected the most active compounds to study their effect on the cell cycle. Cell cycle analysis showed that all of the compounds tested were able to induce cell cycle block at G 2 /M in a concentration-dependent manner. The amount of cell block, measured as a G 1 /G 2 ratio, was correlated significantly (p F 0.001) with apoptosis, as evaluated in the sub-G 1 region (% of DNA fragmentation), thereby suggesting that the G 2 /M-blocked cells underwent apoptosis. To confirm the occurrence of apoptosis in this system, DNA gel agarose electrophoresis was performed and showed the typical ladder pattern.