Description:
<jats:title>Abstract</jats:title><jats:p>Cancer cells produce elevated levels of reactive oxygen species, which has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, in which a prodrug reacts with ROS. However, at low micromolar concentrations of the prodrugs and ROS, the activation is usually inefficient. Herein, we propose and validate a potentially general approach for solving this intrinsic problem of ROS‐dependent prodrugs. In particular, known prodrug 4‐(<jats:italic>N</jats:italic>‐ferrocenyl‐<jats:italic>N</jats:italic>‐benzylaminocarbonyloxymethyl)phenylboronic acid pinacol ester was converted into its lysosome‐specific analogue. Since lysosomes contain a higher concentration of active ROS than the cytoplasm, activation of the prodrug was facilitated with respect to the parent compound. Moreover, it was found to exhibit high anticancer activity in a variety of cancer cell lines (IC<jats:sub>50</jats:sub>=3.5–7.2 μ<jats:sc>m</jats:sc>) and in vivo (40 mg kg<jats:sup>−1</jats:sup>, NK/Ly murine model) but remained weakly toxic towards non‐malignant cells (IC<jats:sub>50</jats:sub>=15–30 μ<jats:sc>m</jats:sc>).</jats:p>