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.
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 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.