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Usnic acid derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1

Abstract

The synthesis of (+)-usnic acid derivatives is described. The derivatives contain one or two cyano groups, connected to the acetophenone fragment of dibenzofuran core by linkers of different length and character, or some other modifications. The influence of these compounds on the activity of recombinant human tyrosyl-DNA phosphodiesterase 1 and MCF-7 tumor cells’ viability has been estimated. The data indicate a distinct dependence of functional characteristics of the compounds on their structure.

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Abbreviations

Tdp1:

tyrosyl-DNA phosphodiesterase 1

Тор1:

topoisomerase 1

UA:

usnic acid

FAM:

fluorescein

BHQ1 (Black Hole Quencher 1):

fluorescence quencher

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Correspondence to A. L. Zakharenko.

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Original Russian Text © A.L. Zakharenko, O.A. Luzina, D.N. Sokolov, O.D. Zakharova, M.E. Rakhmanova, A.A. Chepanova, N.S. Dyrkheeva, O.I. Lavrik, N.F. Salakhutdinov, 2017, published in Bioorganicheskaya Khimiya, 2017, Vol. 43, No. 1, pp. 97–104.

The paper is based on the materials of the “Chemical Biology 2016” conference; Novosibirsk, Russia, July 24–29, 2016.

The authors contributed equally to the work.

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Zakharenko, A.L., Luzina, O.A., Sokolov, D.N. et al. Usnic acid derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1. Russ J Bioorg Chem 43, 84–90 (2017). https://doi.org/10.1134/S1068162017010125

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  • DOI: https://doi.org/10.1134/S1068162017010125

Keywords

  • tyrosyl-DNA phosphodiesterase 1
  • tyrosyl-DNA phosphodiesterase 1 inhibitors
  • usnic acid