Ferrocene conjugates linked by 1,2,3-triazole and their Zn(II) and Cu(II) complexes: Synthesis, characterization and biological activity

Ferrocene derivatives with mono- (8a-c) and bis-1,2,3-triazolyl (9 and 10a-13c) chelating groups were synthesized by regioselective copper(I)-catalysed 1,3-dipolar cycloaddition of terminal alkynes with ferrocene azides. Metal complexes of the ligands were prepared with Cu(II) and Zn(II) salts. Crystal structures of ligands 9 and 11a were determined, as well as the structures of complexes [Cu(8a)(2)](CF3SO3)(2) (8a(Cu)) and [Cu(8c)(2)(CH3OH)(2)](BF4)(2) (8c(Cu)). In addition to NMR and UV-Vis spectroscopy, the metal complexes were characterized by cyclic voltammetry. The cytotoxic effect of ferrocene conjugates and their Zn(II) and Cu(II) complexes was explored, and cell cycle analysis was performed. The complex [Cu(8c)(2)](CF3SO3)(2) showed the most prominent and selective cytotoxicity on cervical carcinoma (HeLa), ovarian cancer (MES-OV), non-small cell lung cancer (A549) and breast carcinoma (MDA-MB-231) cells. This complex increased cell population in the S and G(2)/M phase of the cell cycle, which was accompanied by an increase of the cells present in the sub-G(0)/G(1) fraction.