Study of the Ability of a New Usnic Acid Derivative to Inhibit Tdp1 and Tdp2, and Sensitise the Effect of Antitumour Drugs
A. S. FILIMONOV1, A. L. ZAKHARENKO2, A. A. CHEPANOVA2, O. A. LUZINA1, N. S. DYRKHEEVA2, N. F. SALAKHUTDINOV1, O. I. LAVRIK2
1Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
Keywords: usnic acid, usnic acid derivatives, Tdp1 inhibitor, anti-tumor therapy, sensibilization, temozolomid, olaparib
Pages: 707–714
Abstract
A new usnic acid derivative containing cyanethyl and isoniazid fragments is synthesised. The compound inhibits the activity of DNA repair enzyme Tdp1 with IC50 = 1.2 μM, is inactive against Tdp2 and does not affect cell survival for a panel of passaged cell lines in the concentration range up to 20 μM. It is shown that the compound in combinations with the certain concentrations of antitumour drugs can sensitise the effect of antitumour drugs olaparib and temozolomide on some cell lines.
DOI: 10.15372/CSD2023520
EDN: FNLRUE
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