Abstract:
: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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Colley HE,Muthana M,Danson SJ,Jackson LV,Brett ML,Harrison J,Coole SF,Mason DP,Jennings LR,Wong M,Tulasi V,Norman D,Lockey PM,Williams L,Dossetter AG,Griffen EJ,Thompson MJdoi
10.1021/acs.jmedchem.5b01312subject
Has Abstractpub_date
2015-12-10 00:00:00pages
9309-33issue
23eissn
0022-2623issn
1520-4804journal_volume
58pub_type
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