Synthetic Design and Biological Evaluation of New p53-MDM2 Interaction Inhibitors Based on Imidazoline Core

基于咪唑啉核心的新型p53-MDM2相互作用抑制剂的合成设计及生物学评价

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作者:Daniil R Bazanov, Nikolay V Pervushin, Egor V Savin, Michael D Tsymliakov, Anita I Maksutova, Victoria Yu Savitskaya, Sergey E Sosonyuk, Yulia A Gracheva, Michael Yu Seliverstov, Natalia A Lozinskaya, Gelina S Kopeina

Abstract

The use of p53-MDM2 inhibitors is a prospective strategy in anti-cancer therapy for tumors expressing wild type p53 protein. In this study, we have applied a simple approach of two-step synthesis of imidazoline-based alkoxyaryl compounds, which are able to efficiently inhibit p53-MDM2 protein-protein interactions, promote accumulation of p53 and p53-inducible proteins in various cancer cell lines. Compounds 2l and 2k cause significant upregulation of p53 and p53-inducible proteins in five human cancer cell lines, one of which possesses overexpression of MDM2.

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