TAXOIDS - STRUCTURAL AND EXPERIMENTAL PRO PERTIES

Paclitaxel (Taxol(R)) and docetaxel (Taxotere(R)) are the first repres entatives of a new class of antitumor compounds. These two taxoids are clinically active against breast, ovarian and lung cancers. Taxoids a re highly complex diterpenoids form natural origin. Preclinical and cl inical developments have been made possible after a long and sustained chemical effort: paclitaxel is extracted from the barks of the Pacifi c yew tree Taxus brevifolia whereas docetaxel is prepared by hemisynth esis starting from 10-deacetyl-baccatin III, an inactive precursor fou nd in the needles of the European yew tree Taxus baccata. These two dr ugs are active in various in vitro and in vivo preclinical models (cel l lines, cloning of human tumor stem cells, murine grafted tumors, hum an xenografts). Taxoids constitute a new class of antimitotic agents d ifferent from vinca-alkaloids: on the one hand, paclitaxel and docetax el can be considered as inhibitors of the reaction of depolymerization of microtubules into tubulin; on the other hand, vinca-alkaloids inhi bit reaction of polymerization of tubulin into microtubules. An active program of medicine chemistry is done in various pharmaceutical and a cademic Institutions with two objectives: knowledge of structure-activ ity relationships and selection of new candidates for clinical trials.