Biologically Active Trifluoromethyl-Substituted Metallocene Triazoles: Characterization, Electrochemistry, Lipophilicity, and Cytotoxicity

We report the facile synthesis of four different trifluoromethylated metallocene triazoles and their biological evaluation (M = Fe and Ru). The cytotoxicity of all compounds was evaluated using MCF-7, HT-29, PT-45 and GM5657 cells and IC50 values as low as 33 mu M were found. It was shown that the metallocene moiety is crucial for the cytotoxic effect. The electrochemical behavior of triazoles 36 was investigated by cyclic voltammetry. These electrochemical measurements revealed that all triazoles are less prone to oxidation than ferrocene. Moreover, Log?P determination by RP-HPLC showed increased lipophilicity for the fluorinated derivatives with Log?P values up to 3.8. Furthermore, successful bioconjugation could be achieved by coupling triazole 7 to the amino acid L-leucine.