Recent progress in the development of tubulin inhibitors as antimitotic antitumor agents.
Tubulin protein is a major target of drug molecules, and consequently, tubulin inhibitors have attracted great attention as antimitotic antitumor agents for chemotherapeutic use. Hundreds of synthetic or semisynthetic tubulin inhibitors have been discovered and developed recently that are related to the natural products colchicine, vinblastine, and taxol. Representatives include allothiocolchicinoids, vinorelbine, and taxotere. This review will describe the recent progress being made in the development of novel antimitotic antitumor tubulin inhibitors. The emphasis has been placed on related research in the author's laboratory, including development of colchicine derivatives and other colchicine binding site drugs, such as flavonoids and quinolone derivatives. Syntheses and modifications of novel compounds, biological activity evaluation, and structural activity relationships will be discussed as well. Further research will undoubtedly lead to the discovery of additional tubulin inhibitors that have potential for use as anticancer drugs.
Shi
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Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
Chen
K
K
Morris-Natschke
S L
SL
Lee
K H
KH
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical; D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry; D015195:Drug Design; D005419:Flavonoids / Q000737:chemistry; D008938:Mitosis; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism; D015363:Quinolones / Q000737:chemistry; D050257:Tubulin Modulators; D014748:Vinca Alkaloids / Q000737:chemistry* / Q000378:metabolism
D000970:Antineoplastic Agents; D005419:Flavonoids; D015363:Quinolones; D050257:Tubulin Modulators; D014748:Vinca Alkaloids; D017239:Paclitaxel; D003078:Colchicine