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Molecular Features of the Interaction of Colchicine and Related Structures with Tubulin

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The Role of Microtubules in Cell Biology, Neurobiology, and Oncology

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Colchicine is one of the oldest known antimicrotubule drugs. It exerts its biological effects by binding to a single site on the β-subunit of the tubulin heterodimer. The resulting colchicine-tubulin complex substiochiometrically inhibits tubulin assembly and suppresses microtubule dynamics. A large number of molecules with significant structural diversity interact with the colchicine site on tubulin; literally hundreds of potential colchicine site ligands have been synthesized and tested in the hopes of finding a better clinical agent. In spite of the wealth of data, an understanding of the structure-activity relationship for these colchicine site ligands remains elusive. Colchicine site drugs are believed to act as a common mechanism, which has been studied extensively in the case of colchicine but much less studied for other ligands. In this review, the molecular mechanisms by which colchicine and closely related structures interact with tubulin are explored. Thermodynamic, kinetic, and structure-activity analyses as well as more recent structural information about the ligand-receptor complex are discussed.

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Authors and Affiliations

  1. Department of Chemistry, State University of New York at Binghamton, Binghamton, NY

    Susan L. Bane PhD

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  1. Susan L. Bane PhD
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  1. Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD

    Tito Fojo MD, PhD

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© 2008 Humana Press, Totowa, NJ

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Bane, S.L. (2008). Molecular Features of the Interaction of Colchicine and Related Structures with Tubulin. In: Fojo, T. (eds) The Role of Microtubules in Cell Biology, Neurobiology, and Oncology. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-336-3_11

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  • DOI: https://doi.org/10.1007/978-1-59745-336-3_11

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