Biotechnological production of taxol and related taxoids: current state and prospects.
Taxol is one of the most effective anti-cancer drugs ever developed. The natural source of taxol is the inner bark of several Taxus species, but it accumulates at a very low concentration and with a prohibitively high cost of extraction. Another problem is that the use of inner bark for taxol production implies the destruction of yew trees. For all these reasons, the growing demand for taxol greatly exceeds the supply that can be sustained by isolation from its natural source and alternative sources of the drug are being sought. Although taxol has been prepared by total synthesis, the process is not commercially viable. Taxol can also be semisynthetically produced via the conversion of baccatin III or 10-deacethylbaccatinIII found in Taxus needles but the cost and difficulty of the extraction process of the semisynthetic precursors are also very high. The most promising approach for the sustainable production of taxol and related taxoids is provided by plant cell cultures at an industrial level. Taxol is currently being clinically used against different tumour processes but due to the difficulty of its extraction and formulation, as well as the growing demand for the compound, new taxol analogues with improved properties are being studied. In this revision we discuss current research in the design of new taxol-related compounds, the chemical structure/anti-cancer activity relationship and new formulations of the drug. We also consider the optimizing strategies to improve taxol and related taxoid production in cell cultures, as well as the current knowledge of taxol metabolism, all of which are illustrated with examples, some of them from our own research.
Expósito
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O
Secció de Fisiologia Vegetal, Facultat de Farmacia, Universitat de Barcelona, Avda. Diagonal 643, E-08028 Barcelona, Spain.
Bonfill
M
M
Moyano
E
E
Onrubia
M
M
Mirjalili
M H
MH
Cusidó
R M
RM
Palazón
J
J
D018929:Cell Culture Techniques; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D017239:Paclitaxel / Q000138:chemical synthesis*; D010944:Plants / Q000378:metabolism; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis*
D043823:Taxoids; D017239:Paclitaxel