Dehydroabietylamine Ureas and Thioureas as Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Enhance the Antitumor Effect of Temozolomide on Glioblastoma Cells

Dehydroabietylamine Ureas and Thioureas as Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Enhance the Antitumor Effect of Temozolomide on Glioblastoma Cells Full article

Journal

Journal of Natural Products
ISSN: 0163-3864

Output data

Year: 2019, Volume: 82, Number: 9, Pages: 2443-2450 Pages count : DOI: 10.1021/acs.jnatprod.8b01095

Authors

Kovaleva Kseniya ^1,2 , Oleshko Olga ² , Mamontova Evgeniya ³ , Yarovaya Olga ^1,2 , Zakharova Olga ³ , Zakharenko Alexandra ³ , Kononova Alena ² , Dyrkheeva Nadezhda ³ , Cheresiz Sergey ^2,4 , Pokrovsky Andrey ² , Lavrik Olga ^2,3 , Salakhutdinov Nariman ^1,2

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk 630090, Russia
2	(Данные Web of science) Novosibirsk State Univ, Novosibirsk 630090, Russia
3	(Данные Web of science) Russian Acad Sci, Siberian Branch, Novosibirsk Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia
4	(Данные Web of science) State Sci Res Inst Physiol & Basic Med, POB 237, Novosibirsk 630117, Russia

A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors was found among resin acid derivatives. Several novel ureas and thioureas derived from dehydroabietylamine were synthesized and tested for TDP1 inhibition. The synthesized compounds showed IC50 values in the range of 0.1 to 3.7 mu M and demonstrated low cytotoxicity against the human tumor cell lines U-937, U-87MG, MDA-MB, SK-Me18, A-549, MCF7, T98G, and SNB19. Several compounds showed enhancement of the cytotoxic activity of the alkylating agent temozolomide, which is used as a first line therapy against glioblastoma (GBM), in the GBM cell lines U-87MG and SNB19.

Kovaleva K. , Oleshko O. , Mamontova E. , Yarovaya O. , Zakharova O. , Zakharenko A. , Kononova A. , Dyrkheeva N. , Cheresiz S. , Pokrovsky A. , Lavrik O. , Salakhutdinov N.
Dehydroabietylamine Ureas and Thioureas as Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Enhance the Antitumor Effect of Temozolomide on Glioblastoma Cells
Journal of Natural Products. 2019. V.82. N9. P.2443-2450. DOI: 10.1021/acs.jnatprod.8b01095 WOS Scopus РИНЦ

Published online:	Aug 20, 2019
Published print:	Sep 27, 2019

Web of science	WOS:000488424000009
Scopus	2-s2.0-85071862995
Elibrary	41683948
OpenAlex	W2969529236