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Author Spotlight: Purifying High-Quality Tubulin to Study Protein Dynamics and Therapeutic Applications
Published on: October 11, 2024
Tubulin-binding dibenz[c,e]oxepines: Part 2. Structural variation and biological evaluation as tumour vasculature
Steven B Rossington1, John A Hadfield2, Steven D Shnyder3
1School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Abstract:
5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown, necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological properties of 1 and related compounds can be attributed to their ability to inhibit microtubule assembly at the micromolar level, by binding reversibly to the same site of the tubulin αβ-heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4.
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