The Chemistry and Biology of Antimitotic Chalcones and Related Enone Systems

Nicholas   J.   Lawrence; Alan   T.   McGown

doi:10.2174/1381612053764733

Abstract

The development of combretastatin as an antimitotic agent has led to an enormous effort to design other tubulin-targeting agents. The intriguing discovery that combretastatin A-4 phosphate causes selective damage to tumor vasculature has stimulated even more activity in this field. This attention to tubulin binding agents and their antivasculature activity is highly likely to lead to significant clinical advances for the treatment of cancer. This review focuses on the development of ketones as tubulin-binding agents such as chalcones and related enones as surrogates of combretastatin and colchicine.

Keywords: combretastatins, microtubules, tumor vascular network, x-ray diffraction, mtt assay, diffusion crystallization, enone system, tubulin polymerisation, flavanoids, bioassay-guided fractionation