ABSTRACT
A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, were synthesized and evaluated. The most potent compound in this series, compound 3, which structurally resembles the potent anti-microtubule agent combretastatin A-4, inhibited tubulin polymerization and showed potent growth inhibitory activities on both prostate and breast cancer lines with IC50 values in the low nanomolar range.
Subject(s)
Antineoplastic Agents/chemical synthesis , Drug Design , Tubulin Modulators/chemical synthesis , Tubulin/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Bibenzyls/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Polymerization/drug effects , Tubulin/chemistry , Tubulin Modulators/chemistry , Tubulin Modulators/pharmacologyABSTRACT
A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, was synthesized and evaluated. The most potent compound in this series, compound 7, structurally resembles the potent anti-microtubule agent Combretastatin A-4, inhibited tubulin polymerization, and showed potent growth inhibitory activities on both prostate and breast cancer lines with IC(50) values in low to subnanomolar range.
