Events 7th International Electronic Conference on Medicinal Chemistry

Event submissions

Published

10.3390/ECMC2021-11415

This submission belongs to the session S4. Fighting cancers of the event 7th International Electronic Conference on Medicinal Chemistry

Published date

02 Nov, 2021

Academic Editor

Jean Jacques Vanden Eynde

Citation

Aleksandr Filimonov, Olga Luzina, Nadezhda Dyrkheeva, Olga Lavrik, Nariman Salakhutdinov, The inhibitors of DNA repair enzymes based on usnic acid, in Proceedings of 7th International Electronic Conference on Medicinal Chemistry, 1 November–30 November 2021, MDPI: Basel, Switzerland, doi: 10.3390/ECMC2021-11415

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The inhibitors of DNA repair enzymes based on usnic acid

Aleksandr Filimonov ¹

Olga Luzina ¹

Nadezhda Dyrkheeva ²

Olga Lavrik ²

Nariman Salakhutdinov ¹

1. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 630090, Russian Federation.

2. Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russia

Abstract

The search of new DNA repair enzymes inhibitors is a promising approach of modern pharmacology and one of the ways to increase cancer therapy effectiveness, especially for drug resistant tumors. At the same time the development of new compounds that effectively inhibit activity of various DNA repair enzymes is not an easy task. In the present work an attempt was made to synthesize dual or triple inhibitors of Tyrosyl-DNA-phosphodiesterase 1 and 2 (Tdp1 and 2) and Poly(ADP-ribose)polymerase 1 (PARP1).

The natural compound usnic acid 1 is a widespread secondary metabolite of lichens, the chemical transformation of which previously produced compounds with inhibitory activity against the DNA repair enzyme - Tdp1.

In this work, we have synthesized a number of usnic acid thioesters 2 that differ in the structure of the sulfur atom substituent and have studied their inhibitory activity to the repair enzymes Tdp1, Tdp2 and PARP1. Among the studied compounds, both compounds that are selective Tdp1 inhibitors, as well as dual (Tdp1 and PARP1) and triple inhibitors (Tdp1, Tdp2 and PARP1) were identified. The type of Tdp1 inhibition for the obtained compounds has been found to be uncompetitive.

This study was funded by Russian Foundation for Basic Research 19-415-540002

Keywords

Tdp1

Tdp2

PARP1

dual inhibitors

triple inhibitors

usnic acid

thioethers.

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