Correlations between the in vitro antiproliferative activity, structure and thermal stability of some macrocyclic dinuclear Cu(II) complexes

Abstract

Seven macrocyclic dinuclear Cu(II) complexes with tpmc = = N,N ',N '',N'''-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane of coordination formulae [Cu(2)tpmc](ClO4)(4) (1), [Cu-2(X)tpmc](ClO4)(3)center dot nH(2)O, X= F-, n = 0 (2), X = Cl-, n = 1 (3), X = Br-, n = 0 (4), X= I-, n = 1 (5), X = = NO2-, n = 0 (6), [Cu-2(NCS)(2)tpmc](ClO4)(2) (7) were evaluated for their cytotoxic activity against human cervix adenocarcinoma (HeLa), human melanoma (Fem-x) and human colon carcinoma (LS174) cell lines. The results were compared with the corresponding data for the cis-diamminedichloridoplafinum(H) (CDDP) as referent cytostatic, as well as with the free ligands and the solvent dimethyl sulfoxide (DMSO) as controls. The complexes showed considerable antiproliferative effect, although significantly less than CDDP. The thermal decomposition pattern of the complexes was determined by simultaneous TG/DSC measurements. The thermal stability of the compounds 2-7 followed the trend of their antiproliferative activity against the HeLa cell line, as well as their corresponding stability constants. The highest thermal stability and cytotoxicity belonged to complex [Cu(2)tpmc](ClO4)(4), with no anionic co-ligand. Complex [Cu-2(NO2)tpmc](ClO4)(3) exhibited a selective cytotoxicity against LS174 cells, at the level of the most active [Cu(2)tpmc](ClO4)(4).