Synthesis and biological evaluation of naphthoquinone phenacylimidazolium derivatives. (1st June 2021)

• Record Type: Journal Article
• Authors: Yuan, Jing; Liu, Zhanxiong; Zhang, Zhenfeng; Yan, Deyue; Zhang, Wanbin
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 41(2021)
• Publication Date: 2021-06-01
• Subjects: Naphthoquinone -- Imidazolium -- Phenacyl -- Antitumor -- Antiproliferative; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.127977
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 256-fold 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.