Synthetic Design and Biological Evaluation of New p53-MDM2 Interaction Inhibitors Based on Imidazoline Core
Daniil R. Bazanov, Nikolay V. Pervushin, Egor V. Savin, Michael D. Tsymliakov, Anita I. Maksutova, Viktoriia Yu. Savitskaya, S. E. Sosonyuk, Yulia A. Gracheva, M. 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.