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Medical Sciences Forum
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7 November 2022

Methoxyphenyl Imidazolines as Potential Activators of p53 †

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1
Department of Chemistry, M. V. Lomonosov Moscow State University, 119992 Moscow, Russia
2
Department of Medicine, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Presented at the 8th International Electronic Conference on Medicinal Chemistry, 1–30 November 2022; Available online: https://ecmc2022.sciforum.net/.
This article belongs to the Proceedings The 8th International Electronic Conference on Medicinal Chemistry

Abstract

The use of p53-MDM2/X inhibitors is a prospective strategy in anti-cancer therapy for tumors with wild type p53 protein. In our study, new low-molecular-weight inhibitors of the p53-mdm2 interaction have been proposed. The two-step synthesis of the imidazoline core with subsequent modifications for the nitrogen atom was carried out. New molecules caused the accumulation of p53 protein levels more than seven times than in comparison with the control. The accumulation of proapoptotic proteins such as p21 and PUMA has also been investigated, and the mechanism of cell death has been shown.
Keywords:
p53; nutlin; mdm2; mdmx; imidazoline

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/ECMC2022-13494/s1.

Author Contributions

Investigation D.R.B., N.V.P.; Conceptualization N.A.L., G.S.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Russian Science Foundation, grant number 22-23-20141.

Institutional Review Board Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.
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