Add time:09/05/2019 Source:sciencedirect.com
Ru(η6-arene) complexes of epidermal growth factor receptor (EGFR) inhibiting tyrphostins 1a and 1b were prepared, characterized and tested for DNA interaction and bioactivity in four human tumor cell lines. The intrinsic cytotoxicity and cell line selectivity of o-hydroxyanisol 1a was greatly enhanced in its Ru(η6-p-cymene) complex 2a and in its Ru(η6-toluene) complex 3a. Complex 2a was particularly efficacious against multi-drug resistant EGFR(+) MCF-7/Topo breast carcinoma cells and also against mTOR-dependent EGFR(−) HL-60 leukemia cells. Complex 3a showed enhanced activity only against 518A2 melanoma cells and HL-60 cells, which are both known to express the mTOR protein. DNA was strongly metallated (ca. 1.7–2%) by all new Ru complexes without undergoing topological changes. Apparently, by complexation to Ru fragments tyrphostin derivatives can address additional biological targets in a manner instrumental to antitumoral strategies.
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