Biological activity and cellular uptake of [Ru(η5-C5H5)(PPh3)(Me2bpy)][CF3SO3] complex

Anticancer activity of the new [Ru(η5-C5H5)(PPh3)(Me2bpy)][CF3SO3] (Me2bpy = 4,4′-dimethyl-2,2′-bipyridine) complex was evaluated in vitro against several human cancer cell lines, namely A2780, A2780CisR, HT29, MCF7, MDAMB231 and PC3. Remarkably, the IC50 values, placed in the nanomolar and sub-micromolar range, largely exceeded the activity of cisplatin. Binding to human serum albumin, either HSA (human serum albumin) or HSAfaf (fatty acid-free human serum albumin) does not affect the complex activity. Fluorescence studies revealed that the present ruthenium complex strongly quench the intrinsic fluorescence of albumin. Cell death by the [Ru(η5-C5H5)(PPh3)(Me2bpy)][CF3SO3] complex was reduced in the presence of endocytosis modulators and at low temperature, suggesting an energy-dependent mechanism consistent with endocytosis. On the whole, the biological activity evaluated herein suggests that the complex could be a promising anticancer agent.

Cytotoxicity is reduced by several endocytosis inhibitors (MDC, PAO, Ami, and CLQ) at low temperature, showing that cellular uptake mechanism is consistent with endocytosis.Figure optionsDownload as PowerPoint slideHighlights
► New "RuCp" compound with outstanding anticancer properties.
► Albumin can be a vehicle of transport of this compound in the blood serum.
► Binding to albumin does not affect citotoxicity.
► Endocitosys was found the major cellular uptake mechanism.