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

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.

SUBMITTER: Bazanov DR

PROVIDER: S-EPMC9027661 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Bazanov Daniil R DR Pervushin Nikolay V NV Savin Egor V EV Tsymliakov Michael D MD Maksutova Anita I AI Savitskaya Victoria Yu VY Sosonyuk Sergey E SE Gracheva Yulia A YA Seliverstov Michael Yu MY Lozinskaya Natalia A NA Kopeina Gelina S GS

Pharmaceuticals (Basel, Switzerland) 20220402 4

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 <b>2l</b> and <b>2k</b> cause significant upregulation of p53 and p53-inducible proteins ...[more]

PMID: 35455441

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