Ferricenium complexes: A new type of water-soluble antitumor agent

Summary The antitumor activity of a series of iron complexes, i.e., of ferrocene Cp₂Fe], of tetrachloroferrates(III) R₄N]⁺FeCl₄]^-, and of ferricenium complexes Cp₂Fe]⁺X^- (X^-=FeCl₄]^-, 1/2Cl₃FeOFeCl₃]^2-, H₅Mo₇O₂₄]^-·2H₂O, 2,4,6-(NO₂)₃C₆H₂O]^-, or CCl₃COO]^-·2 CCl₃COOH) was investigated against EAT in CF1 mice. Whereas ferrocene and the ammonium tetrachloroferrates(III) did not show recognizable tumor-inhibiting activity, such activity was exhibited by the water-soluble, salt-like ferricenium complexes; the best antineoplastic properties, with optimum cure rates of 100%, were found for ferricenium picrate and ferricenium trichloroacetate.The ferricenium compounds are the first iron complexes for which antineoplastic activity has now been shown. They represent a new type of antitumor agent insofar as they differ fundamentally from known inorganic and organometallic antitumor agents (a) by their ionic, salt-like character, which is responsible for their high water solubility, and (b) by the absence of a cis-dihalometal moiety; this moiety has been recognized as important for the intracellular action of other known inorganic cytostatics.Abbreviations Cp C₅H₅, cyclopentadienyl ring ligand - EAT Ehrlich ascites tumor - IP intraperitoneal(ly) - p.t.t. post transplantationem tumoris Supported by the Fonds der Chemischen Industrie and by Council, University of the Witwatersrand