Ferrocenylalkyl nucleobases (1-14) were prepared via the reaction of the α-(hydroxy)alkyl ferrocenes FcCHR(OH) (Fc = ferrocenyl; R = H, Me, Et, Ph) with thymine, cytosine, iodo-cytosine and adenine in DMSO at 100• C, yields being 50-80%. The antitumor activities of ferrocenylmethyl thymine (1) against solid tumor models, carcinoma 755 (Ca755) and Lewis lung carcinoma (LLC) were studied in vivo. Therapeutic synergism of antitumor activity against LLC was demonstrated in the case of combined application of compound 1 with anticancer drug cyclophosphamide.

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We analyzed the research data on antitumor effects of a wide range of ferrocene compounds and discussed possible mechanisms of their bioactivities. Current trends in the study of antican cer effects of ferrocene derivatives were considered. Promising ways in the design of low toxicity anticancer ferrocene based drugs of new generation were outlined. * Dedicated to the 60th anniversary of the A. N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences (INEOS RAS). The review was written on the initiative and with the active participation of Yu. S. Nekrasov who served with good faith and fidelity for INEOS RAS for more than 40 years. † Deceased.

aThe toxicity of ferrocenylethyl benzotriazole (1) and other ferrocene compounds including ferrocenylmethyl benzimidazoles (4,5,6,11), ferricenium salts (3,9,10) and ferrocenylmethyl adenine (7), was studied. All ferrocene complexes under investigation showed low or medium toxicities. On the basis of an earlier model of chemical carcinogenesis, the antitumor activity of ferrocenylalkyl azoles 1, 8 and ferricenium salts 9, 10 was studied in vivo in the so-called sub-capsular test on human tumors. This effectiveness was compared with that of cisplatin. A series of ferrocenylalkyl azoles were synthesized by interacting azoles either with α-hydroxyalkyl ferrocenes FcC(OH)R 1 R 2 in organic solvent in the presence of aqueous HBF 4 in quantitative yields or with trimethyl(aminomethyl)ferrocene iodide in an aqueous-basic medium in good yields. The X-ray determinations of molecular and crystal structures of α-(1-benzotriazolyl)ethylferrocene (1) and α-(1-naphthatriazolyl)ethylferrocene (12) were performed.

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