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Combretastatin A-4 Analogues as Antimitotic Antitumor Agents

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Tubulin protein is a major target for anticancer drug discovery. As a result, antimitotic agents constitute an important class of the current anticancer drugs. Hundreds of tubulin inhibitors, naturally occurring, semisynthetic or synthetic, have been reported. Among these, combretastatin A-4 (CA-4), isolated from a South African tree Combretum caffrum, is one of the most potent antimitotic agents. CA-4 shows strong cytotoxicity against a variety of cancer cells, including multi-drug resistant cancer cell lines. It has also been demonstrated to exert highly selective effects in proliferating endothelial cells. CA-4 disodium phosphate (CA4DP), a water-soluble prodrug of CA- 4, shows potent antivascular and antitumor effects in a wide variety of preclinical tumor models. Consequently, a number of CA-4 analogues has been synthesized and evaluated. In this paper, the structure-activity relationships and pharmacological properties of the CA-4 derivatives as a class of potent antimitotic anticancer agents are reviewed and discussed.
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Keywords: antimitotic agents; antivascular activity; combretastatin a-4; combretum caffrum; structure-activity relationships

Document Type: Review Article

Affiliations: Department of Biomedical Sciences, University of Rhode Island, 41-Fogarty Hall, Lower College Road, Kingston, RI 02881, USA.

Publication date: 2003-09-01

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