Synthesis of 7- and 10-spermine conjugates of paclitaxel and 10-deacetyl-paclitaxel as potential prodrugs

Efficient syntheses of two taxol analogs hearing the linear polyamine spermine at 7- and 10-positions of paclitaxel and 10-deacetyl-paclitaxel have been developed. These polyamine-taxol-conjugates were isolated as water soluble difluoride salts. The aim of the present work was to introduce a chemical modification into taxol skeleton in order to increase drug selectivity toward tumor cells. The cytotoxic activity of these conjugates was evaluated in MCF7 and MCF7-R cell lines. The observed low cytotoxicity suggests that these conjugates could act as potential prodrugs. (c) 2006 Elsevier Ltd. All rights reserved.