基于咪唑啉核心的新型p53-MDM2相互作用抑制剂的合成设计与生物学评价

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

Department of Chemistry, M. V. Lomonosov Moscow State University, 119992 Moscow, Russia.

Department of Medicine, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia.

Pharmaceuticals (Basel). 2022 Apr 2;15(4):444. doi: 10.3390/ph15040444.

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 and cause significant upregulation of p53 and p53-inducible proteins in five human cancer cell lines, one of which possesses overexpression of MDM2.

对于表达野生型p53蛋白的肿瘤，使用p53-MDM2抑制剂是抗癌治疗中的一种前瞻性策略。在本研究中，我们应用了一种简单的两步合成基于咪唑啉的烷氧基芳基化合物的方法，这些化合物能够有效抑制p53-MDM2蛋白-蛋白相互作用，促进p53和p53诱导蛋白在各种癌细胞系中的积累。化合物和在五种人类癌细胞系中引起p53和p53诱导蛋白的显著上调，其中一种癌细胞系存在MDM2过表达。