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.

Graphical abstractCytotoxicity 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 full-size imageDownload 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.