Synthesis and biological evaluation of naphthoquinone phenacylimidazolium derivatives

In order to expand structural diversity and improve antitumor efficiency, forty new naphthoquinone phenacylimidazolium derivatives were designed, synthesized and evaluated. Good synthetic yields were obtained under mild conditions using easily available starting materials. Cytotoxicity of these compounds was evaluated in vitro against a panel of human tumor cell lines: human breast carcinoma cell lines (MCF-7), human cervical carcinoma cell lines (HeLa), and human lung carcinoma cell lines (A549). Among them, the optimal compound 7m showed splendid antiproliferative activity with low to 50 nM IC50 values against MCF-7 and excellent selectivity of 256fold compared with the normal cell lines L929. Compound 7m induced apoptosis in a dose-dependent manner. Further mechanism experiments showed that compound 7m dramatically inhibited the expression of survivin and activated the pro-apoptotic protein caspase-3. Our results indicated that the structural modification on the 1,3-substituents of naphthoquinone imidazoliums without 2-substituent is also promising to obtain new antitumor compounds.

Automated summary

The newly designed and synthesized naphthoquinone phenacylimidazolium derivatives showed promising antitumor activity in vitro, with compound 7m demonstrating significant antiproliferative effects and selectivity, inducing apoptosis through inhibiting survivin expression and activating caspase-3.