Indole, a core nucleus for potent inhibitors of tubulin polymerization.

Microtubules are the basic components of cell structure, which take part in a wide number of pivotal cellular functions. Drugs that are able to modulate the microtubule assembly either by inhibition of tubulin polymerization or by blocking microtubule disassembly are of great interest in anti-cancer therapy. Several tubulin polymerization inhibitors characterized by the presence of an indole nucleus have been obtained from natural sources or have been prepared by semi-synthesis. In the last decade an ever increasing number of synthetic indoles have been reported. We have reviewed anti-tubulin agents obtained by synthesis having an indole as core nucleus. The synthesis, the biological activity, and the structure - activity relationship aspects of 3-formyl-2-phenylindoles, heterocombretastatins, diarylindoles, 2-aroylindoles, D-24851, 2-aryl-3-aroylindoles, 3-aroyl- and 1-aroylindoles, and arylthioindoles are discussed. (c) 2006 Wiley Periodicals, Inc.