[Taxoids: structural and experimental properties].
Paclitaxel (Taxol) and docetaxel (Taxotere) are the first representatives of a new class of antitumor compounds. These two taxoids are clinically active against breast, ovarian and lung cancers. Taxoids are highly complex diterpenoids form natural origin. Preclinical and clinical developments have been made possible after a long and sustained chemical effort: paclitaxel is extracted from the barks of the Pacific yew tree Taxus brevifolia whereas docetaxel is prepared by hemisynthesis starting from 10-deacetyl-baccatin III, an inactive precursor found in the needles of the European yew tree Taxus baccata. These two drugs are active in various in vitro and in vivo preclinical models (cell lines, cloning of human tumor stem cells, murine grafted tumors, human xenografts). Taxoids constitute a new class of antimitotic agents different from vinca-alkaloids: on the one hand, paclitaxel and docetaxel can be considered as inhibitors of the reaction of depolymerization of microtubules into tubulin; on the other hand, vinca-alkaloids inhibit reaction of polymerization of tubulin into microtubules. An active program of medicine chemistry is done in various pharmaceutical and academic Institutions with two objectives: knowledge of structure-activity relationships and selection of new candidates for clinical trials.
Lavelle
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Centre de recherche de Vitry-Alfortville, Rhône-Poulenc Rorer SA, Vitry-sur-Seine, France.
Combeau
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Commerçon
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D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel