Second generation of Casiopeinas®: A joint experimental and theoretical study

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 fivecoordination 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.

Automated summary

Three novel second generation Casiopeinas complexes were synthesized, characterized, and evaluated for their antiproliferative activity against HeLa and MCF-7 cancer cell lines. By replacing the usual negatively charged secondary ligand with a neutral bidentate ligand, the compounds showed improved hydrophilicity and antiproliferative activity. The study found that the [Cu(4,7-dimethyl-1,10-phenanthroline)(2AMB)(NO3)]NO3 complex was more effective than cisplatin against both cell lines, with structure-activity relationships influenced by molar volume or redox potential.