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Colley, H.E.; Muthana, M.; Danson, S.J.; Jackson, L.V.; Brett, M.L.; Harrison, J.; Coole, S.F.; Mason, D.P.; Jennings, L.R.; Wong, M.; Tulasi, V.; Norman, D.; Lockey, P.M.; Williams, L.; Dossetter, A.G.; Griffen, E.J.; Thompson, M.J. (2015)
Publisher: American Chemical Society
Languages: English
Types: Article
A number of indole-3-glyoxylamides have previously been reported as tubulin polymerization inhibitors, although none has yet been successfully developed clinically. We report here a new series of related compounds, modified according to a strategy of reducing aromatic ring count and introducing a greater degree of saturation, which retain potent tubulin polymerization activity but with a distinct SAR from previously documented libraries. A subset of active compounds from the reported series is shown to interact with tubulin at the colchicine binding site, disrupt the cellular microtubule network, and exert a cytotoxic effect against multiple cancer cell lines. Two compounds demonstrated significant tumor growth inhibition in a mouse xenograft model of head and neck cancer, a type of the disease which often proves resistant to chemotherapy, supporting further development of the current series as potential new therapeutics.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

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