Synthesis And Biochemical Characterization Of Novel Metallo-salphen Derivatives

Abstract

In an effort to find a novel metal complex that can be used in cancer therapy a series of Fe(III)-salphen derivatives were synthesized and then characterized biochemically. Cytotoxicity assay revealed that Fe(III)-salphen derivatives are toxic to human breast cancer (MCF7) and human colon cancer (CCL228) cells at very low concentrations with IC50 values in the range of 0.31 to 1.48 µM, which is much lower than that of Cisplatin (IC50 18 ± 2 µM). Caspase-3/7 assay and nuclear staining revealed that these compounds kill the cells by inducing apoptosis as signified by the condensation and fragmentation of the nucleus and the increased activity of caspase-3/7. Ascorbic acid assay revealed that the Fe(III)-salphen derivative (compound 2, CH3) induces apoptosis by oxidative stress as the viability of compound 2 treated cells was significantly increased by co-treating with ascorbic acid. As cell cycle regulatory genes are overexpressed in tumor cells the expression of cyclins (A, B, D, and E) was evaluated at mRNA levels after treatment of CCL228 cells with compound 2 (CH3) and Cisplatin. The results showed that the toxicity of these compounds is not related to the overexpression of these genes although some cyclins seem to be up-regulated in Cisplatin treated cells.