Chemistry and Biology of Curacin A

Author(s): Peter Wipf, Jonathan T. Reeves, Billy W. Day

Journal Name: Current Pharmaceutical Design

Volume 10 , Issue 12 , 2004

Become EABM
Become Reviewer


Many natural and synthetic compounds bind to tubulin, an ubiquitous globular protein that provides the building blocks for the cellular microtubule network that controls chromosome segregation during mitosis, vesicle movements, intracellular transport of organelles, ciliar and flagellar movement, and maintenance of cell shape. Since the isolation of the antimitotic marine natural product curacin A in 1994, synthetic work on this colchicine-site binding agent has been intense, but only recently have synthetic derivatives been identified that match its potency for tubulin polymerization inhibition and its high level of growth inhibition in cancer cell lines. In addition to several total synthesis efforts, combinatorial libraries were constructed using solution phase and fluorous scavenging approaches. Low watersolubility and lack of chemical stability represent strong detriments for the clinical development of curacin A, but synthetic analogs with improved bioavailability might ultimately probe the paradigm for anticancer efficacy of colchicinesite tubulin binding agents.

Keywords: curacin a, colchicine, tubulin, antimitotic agents, bioisosteres, anticancer activity, sar, natural products

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2004
Page: [1417 - 1437]
Pages: 21
DOI: 10.2174/1381612043384853
Price: $65

Article Metrics

PDF: 10