Erratum: A Preliminary Study of the Toxicological Properties of Selected Polymer-Ferrocene Conjugates

Abstract

Prompted by early observations of the cytotoxic and antineoplastic properties of certain ferrocene and ferricenium derivatives, efforts in this laboratory were focused on the synthesis of carrier-bound ferrocene compounds. Subsequent cell culture tests carried out with selected conjugates obtained in that program showed these polymers to be highly active antiproliferative agents. In the present project toxicological work has been performed in vivo on several ferrocene conjugates in an effort to assess their toxic effects in experimental animals (CD-1 mice). The conjugates, all based on an α,β-DL-polyaspartamide backbone structure, comprise the ferrocene drug model as a terminal on short side chains containing biofissionable amide or ester links for intracellular drug release. The polymers, dissolved in phosphate-buffered saline, have been injected in predetermined concentrations into the vein of the mice, and the maximum tolerated dose (MTD) levels have been determined, the latter referring to the highest dose levels administered that would allow long-term survival of the test animals. For the five conjugates tested, MTD levels range from about 3 to 30 mg Fe/kg or 0.05–0.66 mmol Fe/kg. Compared on a molar metal-to-metal basis with similarly structured platinum conjugates tested previously (MTD, ∼0.14–2.66 mmol Pt/kg), these values are indicative of comparatively high toxicity of the ferrocene polymers. Some implications of these findings are discussed.