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The development of tyrosyl-DNA phosphodyesterase 1 (TDP1) inhibitors based on the amines combining aromatic/heteroaromatic and monoterpenoid moieties. / Mozhaitsev, Evgenii; Suslov, Evgenii; Demidova, Yuliya et al.

In: Letters in Drug Design and Discovery, Vol. 16, No. 5, 01.01.2019, p. 597-605.

Research output: Contribution to journal › Article › peer-review

Harvard

Mozhaitsev, E, Suslov, E, Demidova, Y, Korchagina, D, Volcho, K, Zakharenko, A, Vasil’eva, I, Kupryushkin, M, Chepanova, A, Ayine-Tora, DM, Reynisson, J, Salakhutdinov, N & Lavrik, O 2019, 'The development of tyrosyl-DNA phosphodyesterase 1 (TDP1) inhibitors based on the amines combining aromatic/heteroaromatic and monoterpenoid moieties', Letters in Drug Design and Discovery, vol. 16, no. 5, pp. 597-605. https://doi.org/10.2174/1570180816666181220121042

APA

Mozhaitsev, E., Suslov, E., Demidova, Y., Korchagina, D., Volcho, K., Zakharenko, A., Vasil’eva, I., Kupryushkin, M., Chepanova, A., Ayine-Tora, D. M., Reynisson, J., Salakhutdinov, N., & Lavrik, O. (2019). The development of tyrosyl-DNA phosphodyesterase 1 (TDP1) inhibitors based on the amines combining aromatic/heteroaromatic and monoterpenoid moieties. Letters in Drug Design and Discovery, 16(5), 597-605. https://doi.org/10.2174/1570180816666181220121042

Vancouver

Mozhaitsev E, Suslov E, Demidova Y, Korchagina D, Volcho K, Zakharenko A et al. The development of tyrosyl-DNA phosphodyesterase 1 (TDP1) inhibitors based on the amines combining aromatic/heteroaromatic and monoterpenoid moieties. Letters in Drug Design and Discovery. 2019 Jan 1;16(5):597-605. doi: 10.2174/1570180816666181220121042

Author

Mozhaitsev, Evgenii ; Suslov, Evgenii ; Demidova, Yuliya et al. / The development of tyrosyl-DNA phosphodyesterase 1 (TDP1) inhibitors based on the amines combining aromatic/heteroaromatic and monoterpenoid moieties. In: Letters in Drug Design and Discovery. 2019 ; Vol. 16, No. 5. pp. 597-605.

BibTeX

@article{b4feb5fdb75a454caee495150afea531,
title = "The development of tyrosyl-DNA phosphodyesterase 1 (TDP1) inhibitors based on the amines combining aromatic/heteroaromatic and monoterpenoid moieties",
abstract = "Background: Inhibition of the DNA repair enzyme, tyrosyl-DNA phosphodiesterase 1 (TDP1), may increase the efficacy of cancer drugs that cause damage to tumor cell DNA. Among the known TDP1 inhibitors, there are compounds containing moieties of natural substances, e.g., monoterpenoids. In this work, we synthesized several compounds containing aromatic/ heteroaromatic amines and monoterpenoid groups and assessed their TDP1 inhibition potential. Methods: Structures of all the synthesized compounds were confirmed by1H and13C NMR as well as HRMS. The TDP1 inhibitory activity of the amines was determined by real-time fluorescence oligonucleotide biosensor. Results: The synthesized secondary amines had TDP1 inhibitory activity IC50 in the range of 0.79-9.2 μM. The highest activity was found for (–)-myrtenal derivatives containing p-bromoaniline or m-(trifluoromethyl)aniline residue. Conclusion: We synthesized 22 secondary amines; of these, 17 amines are novel chemical structures. Many of the amines inhibit TDP1 activity in the low micromolar range. Therefore, these compounds are promising for further study of their antiproliferative activity in conjunction with DNA damaging drugs.",
keywords = "Anilines, Cancer, Chemical space, Molecular modeling, Myrtenal, Perillyl aldehyde, Secondary amines, Terpenes, perillyl aldehyde, TOPOISOMERASES, terpenes, EMPIRICAL SCORING FUNCTIONS, myrtenal, BIOLOGICAL EVALUATION, chemical space, PHOSPHODIESTERASE TDP1, DERIVATIVES, ACID, IDENTIFICATION, molecular modeling, PROTEIN-LIGAND DOCKING, POT MYRTENOL AMINATION, secondary amines, cancer, BINDING",
author = "Evgenii Mozhaitsev and Evgenii Suslov and Yuliya Demidova and Dina Korchagina and Konstantin Volcho and Alexandra Zakharenko and Inna Vasil{\textquoteright}eva and Maksim Kupryushkin and Arina Chepanova and Ayine-Tora, {Daniel Moscoh} and J{\'o}hannes Reynisson and Nariman Salakhutdinov and Olga Lavrik",
year = "2019",
month = jan,
day = "1",
doi = "10.2174/1570180816666181220121042",
language = "English",
volume = "16",
pages = "597--605",
journal = "Letters in Drug Design and Discovery",
issn = "1570-1808",
publisher = "Bentham Science Publishers B.V.",
number = "5",

}

RIS

TY - JOUR

T1 - The development of tyrosyl-DNA phosphodyesterase 1 (TDP1) inhibitors based on the amines combining aromatic/heteroaromatic and monoterpenoid moieties

AU - Mozhaitsev, Evgenii

AU - Suslov, Evgenii

AU - Demidova, Yuliya

AU - Korchagina, Dina

AU - Volcho, Konstantin

AU - Zakharenko, Alexandra

AU - Vasil’eva, Inna

AU - Kupryushkin, Maksim

AU - Chepanova, Arina

AU - Ayine-Tora, Daniel Moscoh

AU - Reynisson, Jóhannes

AU - Salakhutdinov, Nariman

AU - Lavrik, Olga

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Inhibition of the DNA repair enzyme, tyrosyl-DNA phosphodiesterase 1 (TDP1), may increase the efficacy of cancer drugs that cause damage to tumor cell DNA. Among the known TDP1 inhibitors, there are compounds containing moieties of natural substances, e.g., monoterpenoids. In this work, we synthesized several compounds containing aromatic/ heteroaromatic amines and monoterpenoid groups and assessed their TDP1 inhibition potential. Methods: Structures of all the synthesized compounds were confirmed by1H and13C NMR as well as HRMS. The TDP1 inhibitory activity of the amines was determined by real-time fluorescence oligonucleotide biosensor. Results: The synthesized secondary amines had TDP1 inhibitory activity IC50 in the range of 0.79-9.2 μM. The highest activity was found for (–)-myrtenal derivatives containing p-bromoaniline or m-(trifluoromethyl)aniline residue. Conclusion: We synthesized 22 secondary amines; of these, 17 amines are novel chemical structures. Many of the amines inhibit TDP1 activity in the low micromolar range. Therefore, these compounds are promising for further study of their antiproliferative activity in conjunction with DNA damaging drugs.

AB - Background: Inhibition of the DNA repair enzyme, tyrosyl-DNA phosphodiesterase 1 (TDP1), may increase the efficacy of cancer drugs that cause damage to tumor cell DNA. Among the known TDP1 inhibitors, there are compounds containing moieties of natural substances, e.g., monoterpenoids. In this work, we synthesized several compounds containing aromatic/ heteroaromatic amines and monoterpenoid groups and assessed their TDP1 inhibition potential. Methods: Structures of all the synthesized compounds were confirmed by1H and13C NMR as well as HRMS. The TDP1 inhibitory activity of the amines was determined by real-time fluorescence oligonucleotide biosensor. Results: The synthesized secondary amines had TDP1 inhibitory activity IC50 in the range of 0.79-9.2 μM. The highest activity was found for (–)-myrtenal derivatives containing p-bromoaniline or m-(trifluoromethyl)aniline residue. Conclusion: We synthesized 22 secondary amines; of these, 17 amines are novel chemical structures. Many of the amines inhibit TDP1 activity in the low micromolar range. Therefore, these compounds are promising for further study of their antiproliferative activity in conjunction with DNA damaging drugs.

KW - Anilines

KW - Cancer

KW - Chemical space

KW - Molecular modeling

KW - Myrtenal

KW - Perillyl aldehyde

KW - Secondary amines

KW - Terpenes

KW - perillyl aldehyde

KW - TOPOISOMERASES

KW - terpenes

KW - EMPIRICAL SCORING FUNCTIONS

KW - myrtenal

KW - BIOLOGICAL EVALUATION

KW - chemical space

KW - PHOSPHODIESTERASE TDP1

KW - DERIVATIVES

KW - ACID

KW - IDENTIFICATION

KW - molecular modeling

KW - PROTEIN-LIGAND DOCKING

KW - POT MYRTENOL AMINATION

KW - secondary amines

KW - cancer

KW - BINDING

UR - http://www.scopus.com/inward/record.url?scp=85071045135&partnerID=8YFLogxK

U2 - 10.2174/1570180816666181220121042

DO - 10.2174/1570180816666181220121042

M3 - Article

AN - SCOPUS:85071045135

VL - 16

SP - 597

EP - 605

JO - Letters in Drug Design and Discovery

JF - Letters in Drug Design and Discovery

SN - 1570-1808

IS - 5

ER -

ID: 21344065