Tyrosyl-DNA Phosphodiesterase 1 Inhibitors: Usnic Acid Enamines Enhance the Cytotoxic Effect of Camptothecin

Tyrosyl-DNA Phosphodiesterase 1 Inhibitors: Usnic Acid Enamines Enhance the Cytotoxic Effect of Camptothecin Full article

Journal

Journal of Natural Products
ISSN: 0163-3864

Output data

Year: 2016, Volume: 79, Number: 11, Pages: 2961-2967 Pages count : 7 DOI: 10.1021/acs.jnatprod.6b00979

Authors

Zakharenko Alexandra ¹ , Luzina Olga ² , Koval Olga ^1,3 , Nilov Dmitry ⁴ , Gushchina Irma ⁵ , Dyrkheeva Nadezhda ¹ , Svedas Vytas ^4,5 , Salakhutdinov Nariman ^2,3 , Lavrik Olga ^1,3

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Branch, Novosibirsk Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia
2	(Данные Web of science) Russian Acad Sci, NN Vorozhtsov Novosibirsk Inst Organ Chem, Siberian Branch, Novosibirsk 630090, Russia
3	(Данные Web of science) Novosibirsk State Univ, Novosibirsk 630090, Russia
4	(Данные Web of science) Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow 119991, Russia
5	(Данные Web of science) Lomonosov Moscow State Univ, Fac Bioengn & Bioinformat, Moscow 119991, Russia

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a repair enzyme for stalled DNA-topoisomerase 1 (Topl) cleavage complexes and other 3'-end DNA lesions. TDP1 is a perspective target for anticancer therapy based on Topl-poison-mediated DNA damage. Several novel usnic acid derivatives with an enamine moiety have been synthesized and tested as inhibitors of TDP1. The enamines of usnic acid showed IC50 values in the range of 0.16 to 2.0 mu M. These compounds revealed moderate cytotoxicity against human tumor MCF-7 cells. These new compounds enhanced the cytotoxicity of the established Topl poison camptothecin by an order of magnitude.

Zakharenko A. , Luzina O. , Koval O. , Nilov D. , Gushchina I. , Dyrkheeva N. , Svedas V. , Salakhutdinov N. , Lavrik O.
Tyrosyl-DNA Phosphodiesterase 1 Inhibitors: Usnic Acid Enamines Enhance the Cytotoxic Effect of Camptothecin
Journal of Natural Products. 2016. V.79. N11. P.2961-2967. DOI: 10.1021/acs.jnatprod.6b00979 WOS Scopus РИНЦ

Published online:	Nov 14, 2016
Published print:	Nov 23, 2016

Web of science	WOS:000394410600023
Scopus	2-s2.0-84999089879
Elibrary	27587089
OpenAlex	W2551275990