Ferrocenes (F168, F169) and fero-sorbitol-citrate (FSC): potential anticancer drugs

We have shown earlier that the iron containing, ferric-sorbitol-citrate complex (FSC) inhibited proliferation of cultured mouse melanoma B16, GHC, KB, HeLa and CaCo2 cells and caused mouse melanoma regression in vivo. This drug did not affect the proliferation of the nonmalignant fibroblast L929 line, human bone marrow-HBS, VERO and HEF cell line. It is also known, that some metallocene derivatives posses antitumour properties resulting principally from their action on the metabolism of DNA, and subsequently, RNA and proteins. We synthesized in our laboratory some ferrocene analogs (F168 and F169) and tested their antiproliferative ability for malignant human carcinoma Hep2 and mouse melanoma F10 cell lines. As control cell lines, human HEF and mice L929 fibroblasts were used. The tested iron substances were very potent in inhibiting the growth of malignant cell lines, whereas they had no significant inhibitory effect on the viability of nonmalignant fibroblasts. The most pronounced growth inhibitory and cytotoxic effect was found in the malignant F10 cells and the most potent was ferrocene F169. Because of their selective effect on malignant cells, the ferric-sorbitol-citrate complex as well as tested ferrocenes will be further investigated and submitted as new antitumour substances.