Medicinal chemistry of paclitaxel and its analogues.
Paclitaxel belongs to the most successful anticancer drugs developed and utilised during the past two decades. Nevertheless, the development of resistance of tumor cells and severe side effects in the patients require further improvement of the drug. In this review, we provide a detailed overview of the state-of-the-art in the medicinal chemistry of paclitaxel and its analogues. A number of strategies have been explored to obtain sufficient amounts of paclitaxel for clinical use from natural resources. Semi-synthesis from its precursor, 10-deacetylbaccatin III, which can be extracted from Taxus leavesturned out as the most appropriate method for commercial production. So far, many paclitaxel derivatives have been synthesized, and their effect on microtubules stabilization and cytotoxicity were investigated in terms of structure-activity relationships (SAR). One of them, docetaxel, was approved as a more potent anticancer agent than paclitaxel towards a variety of tumor types. This review summarizes current possibilities to harvest sufficient amount of drugs from natural sources, including the production of taxanes in bioreactors and synthetic approaches for paclitaxel and its analogues, their mechanism of action and structure-activity relationships. In addition, future developments and perspectives for this class of compounds are outlined.
Fu
Y
Y
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China. yujie_fu2002@yahoo.com
Li
S
S
Zu
Y
Y
Yang
G
G
Yang
Z
Z
Luo
M
M
Jiang
S
S
Wink
M
M
Efferth
T
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel