The Cytotoxic Activity of Macromolecular Ferrocene Conjugates Against the Colo 320 DM Human Colon Cancer Line

Abstract

Water-soluble and biocompatible polymers containing bioreversibly attached ferrocene units as side chain terminals have in recent years attracted interest in drug research. In preliminary screens, polymers of this type have shown high antiproliferative activity against selected human carcinoma cell lines, paired with low in vivo toxicity. They may thus lend themselves as efficacious prodrugs in cancer chemotherapy. Cancers of the intestinal system are known to resist chemotherapeutic treatment. This general lack of sensitivity of the colorectal malignancies prompted us to investigate the in vitro behavior of selected carrier-bound ferrocene prodrugs against the Colo 320 DM cell line, a representative human adenocarcinoma of the colon. The findings of this investigation are reported in the present communication. The carriers 1 to 10 used for conjugation with the metallocene are water-soluble aliphatic polyamides featuring primary or secondary amine functionality as side chain terminals or main chain constituents. By previously developed methodology these amino groups are coupled with the ferrocenylation agent, 4-ferrocenylbutanoic acid, generating the target conjugates 1-Fc to 10-Fc, in which the metallocene is bound through amide or hydrazone links. Cell culture tests are performed by established protocol against the Colo line and, for comparison, also against the HeLa cells. Significantly, while outstanding performance is observed for most of the conjugates against both cell lines, the results indicate activities in the Colo screens to be higher on average than determined in the sensitive HeLa tests.