Enhanced Intracellular Accumulation and Cytotoxicity of Ferrocene-Ruthenium Arene Conjugates
Gelle D., Lamač M., Mach K., Šimková L., Gyepes R., Sommerová L., Martišová A., Bartošík M., Vaculovič T., Kanický V., Hrstka R., Pinkas J.
Coordination of arenophilic Cp*Ru+ (Cp*=η5-C5Me5) fragment to pendant aromatic ring(s) of either benzylferrocene (1) or dibenzylferrocene (2) gave air- and water-stable dinuclear (4) or trinuclear (6) ferrocene-ruthenium conjugates. The complexes were characterized by NMR, ESI-MS, cyclic voltammetry (CV), elemental analysis, and the molecular structure of 4 was established by single crystal X-ray diffraction. Contrary to the starting ferrocenes 1 and 2, conjugates 4 and 6 showed significant in vitro anticancer activity (up to IC50 0.6±0.2 μM) against various cancer cell lines (A2780, SK-OV-3, MDA-MB-231). Differential pulse voltammetry (DPV) showed that the intracellular accumulation of 4 was approximately twice that of 6 in all studied cell lines, which corresponds to a higher cytotoxicity of 4.