LAUSR

Abstract Herein, we present the synthesis, characterization, DFT calculations and in vitro evaluation of antiproliferative activity against HeLa and MCF-7 cancer tumor cell lines of three novel second generation Casiopeinas® complexes. These compounds are characterized by the substitution of the usual negatively charged secondary ligand with a neutral bidentate ligand (2AMB = 2-aminomethylbenzimidazole), in order to improve both hydrophilicity and antiproliferative activity. Geometry for the compounds in this study assumes that complexes present a five-coordination number with a square pyramidal geometry, in which two bidentate ligands are in the plane and a nitrate anion is bonded in the axial position. Among analyzed complexes, only [Cu(4,7-dimethyl-1,10-phenanthroline)(2AMB)(NO3)]NO3 is shown to be more effective than the referenced cisplatin drug, against both HeLa and MCF-7 tumor cell lines. Finally, for studied compounds, structure–activity relationships are strongly determined by either the calculated molar volume (V) or the redox potential (E1/2) of CuII/CuI of the complexes. These results aim to encourage further joint experimental theoretical studies, not only to describe biological activity, but also to predict it.