Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1

Zakharenko, Alexandra L.; Luzina, Olga A.; Chepanova, Arina A.; Dyrkheeva, Nadezhda S.; Salakhutdinov, Nariman F.; Lavrik, Olga I.

doi:10.3390/ijms24065781

Open AccessReview

Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1

by

Alexandra L. Zakharenko

¹,

Olga A. Luzina

^2,*

,

Arina A. Chepanova

¹,

Nadezhda S. Dyrkheeva

¹

,

Nariman F. Salakhutdinov

² and

Olga I. Lavrik

¹

Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia

²

N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2023, 24(6), 5781; https://doi.org/10.3390/ijms24065781

Submission received: 9 February 2023 / Revised: 22 February 2023 / Accepted: 14 March 2023 / Published: 17 March 2023

(This article belongs to the Special Issue DNA Damage, DNA Repair, and Cancer)

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Abstract

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an important repair enzyme that removes various covalent adducts from the 3′ end of DNA. Particularly, covalent complexes of topoisomerase 1 (TOP1) with DNA stabilized by DNA damage or by various chemical agents are an examples of such adducts. Anticancer drugs such as the TOP1 poisons topotecan and irinotecan are responsible for the stabilization of these complexes. TDP1 neutralizes the effect of these anticancer drugs, eliminating the DNA adducts. Therefore, the inhibition of TDP1 can sensitize tumor cells to the action of TOP1 poisons. This review contains information about methods for determining the TDP1 activity, as well as describing the inhibitors of these enzyme derivatives of natural biologically active substances, such as aminoglycosides, nucleosides, polyphenolic compounds, and terpenoids. Data on the efficiency of combined inhibition of TOP1 and TDP1 in vitro and in vivo are presented.

Keywords: natural compound; derivative; TDP1 inhibitors; anticancer therapy; TOP1 inhibitors

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MDPI and ACS Style

Zakharenko, A.L.; Luzina, O.A.; Chepanova, A.A.; Dyrkheeva, N.S.; Salakhutdinov, N.F.; Lavrik, O.I. Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1. Int. J. Mol. Sci. 2023, 24, 5781. https://doi.org/10.3390/ijms24065781

AMA Style

Zakharenko AL, Luzina OA, Chepanova AA, Dyrkheeva NS, Salakhutdinov NF, Lavrik OI. Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1. International Journal of Molecular Sciences. 2023; 24(6):5781. https://doi.org/10.3390/ijms24065781

Chicago/Turabian Style

Zakharenko, Alexandra L., Olga A. Luzina, Arina A. Chepanova, Nadezhda S. Dyrkheeva, Nariman F. Salakhutdinov, and Olga I. Lavrik. 2023. "Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1" International Journal of Molecular Sciences 24, no. 6: 5781. https://doi.org/10.3390/ijms24065781

APA Style

Zakharenko, A. L., Luzina, O. A., Chepanova, A. A., Dyrkheeva, N. S., Salakhutdinov, N. F., & Lavrik, O. I. (2023). Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1. International Journal of Molecular Sciences, 24(6), 5781. https://doi.org/10.3390/ijms24065781

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Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1

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