Water-soluble molybdenocene complexes with both proliferative and antiproliferative effects on cancer cell lines and their binding interactions with human serum albumin.

Abstract

Two water-soluble molybdenocene complexes containing oxygen chelating ligands, maltolato and malonate, have been synthesized to elucidate the role of the ancillary ligands in the molybdenocene cytotoxic activity. The structural characterizations of these species by 1H NMR and IR spectroscopies suggest that both molybdenocene complexes contain the ligands in a bidentate fashion and elemental analysis and mass spectrometry corroborate the proposed formula for the species to be Cp2Mo(malonate) and [Cp2Mo(maltolato)]Cl (Cp is cyclopentadienyl). Metal-albumin binding studies were pursued using UV-vis spectroscopy and cyclic voltammetric techniques. Whereas metal-albumin binding studies using UV-vis spectroscopy did not show any evidence of interaction, cyclic voltammetry experiments showed that molybdenocene complexes may be involved in weak binding interactions with albumin, most likely in hydrophobic interactions. The cytotoxic activities of Cp2Mo(malonate) and [Cp2Mo(maltolato)]Cl alone with Cp2MoCl2 were investigated in HT-29 colon cancer and MCF-7 breast cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay. Cp2Mo(malonate) and [Cp2Mo(maltolato)]Cl showed slight improvement in terms of cytotoxic activity as compared with Cp2MoCl2 in the HT-29 colon cancer cell line, whereas for MCF-7 all the molybdenocene species exhibited a proliferative profile. The molybdenocene-containing chelating ligands showed stronger proliferative effects than Cp2MoCl2. There is no correlation between the binding affinity of molybdenocenes for human serum albumin and cytotoxic activity toward HT-29 and MCF-7 cancer cells.