title: Combretastatin A-4 analogues as antimitotic antitumor agents.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, College of Pharmacy, University of Rhode Island, RI 02881, USA. nhnam@hotmail.com
authors.forename: Nguyen-Hai
authors.initials: NH
authors.lastname: Nam
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D029765:Combretum / Q000737:chemistry*; D008938:Mitosis / Q000187:drug effects; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C058728:fosbretabulin