Abstract
The influence of a number of usnic acid derivatives on auto(polyADP-ribosyl)ation catalyzed by PARP1 and DNA synthesis catalyzed by DNA polymerase β was studied. The derivatives of usnic acid containing aromatic substituents were shown to be moderate inhibitors of PARP1. The presence of both usnic acid tricyclic structure and aromatic substituent at any position of the molecule is a key factor for the inhibitory action. In the case of DNA polymerase β, no relationship between the structure and inhibitory properties has been found with the only exception. Derivatives with modified ring A showed mild activation of DNA synthesis catalyzed by DNA polymerase β.
Keywords: DNA Polymerase β, PARP1, Poly(ADP-ribose)polymerase, Usnic acid, DNA, enzyme, antifungal, carcinoma, malignant, antitumor
Medicinal Chemistry
Title:Influence of Usnic Acid and its Derivatives on the Activity of Mammalian Poly(ADP-ribose)polymerase 1 and DNA Polymerase β
Volume: 8 Issue: 5
Author(s): Alexandra Zakharenko, Dmitry Sokolov, Olga Luzina, Maria Sukhanova, Svetlana Khodyreva, Olga Zakharova, Nariman Salakhutdinov and Olga Lavrik
Affiliation:
Keywords: DNA Polymerase β, PARP1, Poly(ADP-ribose)polymerase, Usnic acid, DNA, enzyme, antifungal, carcinoma, malignant, antitumor
Abstract: The influence of a number of usnic acid derivatives on auto(polyADP-ribosyl)ation catalyzed by PARP1 and DNA synthesis catalyzed by DNA polymerase β was studied. The derivatives of usnic acid containing aromatic substituents were shown to be moderate inhibitors of PARP1. The presence of both usnic acid tricyclic structure and aromatic substituent at any position of the molecule is a key factor for the inhibitory action. In the case of DNA polymerase β, no relationship between the structure and inhibitory properties has been found with the only exception. Derivatives with modified ring A showed mild activation of DNA synthesis catalyzed by DNA polymerase β.
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Zakharenko Alexandra, Sokolov Dmitry, Luzina Olga, Sukhanova Maria, Khodyreva Svetlana, Zakharova Olga, Salakhutdinov Nariman and Lavrik Olga, Influence of Usnic Acid and its Derivatives on the Activity of Mammalian Poly(ADP-ribose)polymerase 1 and DNA Polymerase β, Medicinal Chemistry 2012; 8 (5) . https://dx.doi.org/10.2174/157340612802084225
DOI https://dx.doi.org/10.2174/157340612802084225 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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