Design of ferrocenylseleno-dopamine derivatives to optimize the Fenton-like reaction efficiency and antitumor efficacy

Abstract

In the current study, six ferrocenylseleno-dopamine derivatives with different structural parameters were designed. Among these derivatives, F4b, containing two ferrocene units and a tertiary amine, showed in vitro anticancer activity with IC₅₀ = 2.4 ± 0.4 μM for MGC-803 cells, and its in vivo studies suggested effective antitumor activity in mice bearing an MGC-803 tumor xenograft. Mechanistic study revealed that the cytotoxicity of these ferrocenylseleno-dopamine derivatives is mainly related to the Fenton-like reaction under physiological conditions, and the tertiary amine in F4b can facilitate the H₂O₂ decomposition to generate toxic ˙OH which induces apoptosis through CDK-2 inactivation.