Enantiomeric pairs of copper(II) polypyridyl-alanine complex salts: anticancer studies

The anticancer properties of two previously characterized pairs of optically pure chiral complex salts [Cu(phen)(ala)(H2O)]X center dot xH(2)O (phen = 1.10-phenanthroline; X = NO3 (-); ala: l-alanine (l-ala) 1 and d-alanine (d-ala) 2; and (X = Cl-; ala: l-ala, 3 and d-ala, 4; x = number of lattice water molecules) are reported herein, together with the crystal structure of the d-enantiomer 4. Unlike cisplatin which is ineffective against MCF-7 cancer cells with the absence of caspase-3 protein expression, these two pairs of complex salts were effective against this cell line and they were able to induce an increase in intracellular ROS, loss in mitochondrial membrane potential, cell cycle arrest mainly at SubG1 phase , caspase-9 activation, and caspase-3/caspase-7-independent apoptosis. Screening of 1 on the NCI-60 panel of human cancer cell lines showed that it was effective against most of the cell lines. MTT-NCI modified assay screening was also done on other cancer cell lines, viz. A549, CNE1, and HepG2, and two normal cell lines, viz. MCF-10A and CHANG. The effects of chirality of these Cu(II) compounds, especially the greater selectivity of d-enantiomers over the l-counterparts, on their anticancer properties are also reported herein.