ANTITUMOR EFFECTS OF BINUCLEAR FERROCENE DERIVATIVES

On the basis of an earlier model of chemical carcinogenesis, the antitumor activity of the mono-, bi- and poly-nuclear ferrocene derivatives ferricenium tri-iodide (1), ferricenium tetrachloroferrate (2), 1,1'-diethylferricenium triiodide (3), N-(ferrocenylmethyl)hexamethylenetetramine tetrafluoroborate (4), bis(ferrocenylmetbyl) benzotriazolium tetrafluoroborate (5), bis(ferrocenyl-alpha-ethyl)benzotriazolium tetrafluoroborate (6) and bis(ferrocenylmethyl)-2-methylbenzimidazolium tetrafluoroborate (7), and the oligomer (-Fc-CH2-Fc+-CH2-)7-8-(PF6)7-8 (8) was studied in vivo (Fc=C10H8Fe). The tumor models studied included MCH-11 (mouse sarcoma induced by methylcholantrene), P-815 (mouse mastocytoma of DBA/2 origin) and virus-induced Raucher leukemia (RLV). The cytotoxic effects of these preparations were examined against in vitro cultured normal murine cells (line L-929). The binuclear ferrocene derivatives 5, 6 and 7 inhibited the development of experimental tumors in mice. Ferricenium tri-iodide (1) was effective in Rauscher leukemia. Kinetic dependencies for most complexes had a two-phase character: the region of inhibition of tumorogenesis was followed by a region in which the complexes accelerated the development of this process. The link between the structure of compounds 1-8 and their antitumor effects is discussed.