Open Access
Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy
Тип публикации: Journal Article
Дата публикации: 2019-12-23
scimago Q1
wos Q1
БС1
SJR: 1.273
CiteScore: 9.0
Impact factor: 4.9
ISSN: 16616596, 14220067
PubMed ID:
31878088
Catalysis
Organic Chemistry
Inorganic Chemistry
Physical and Theoretical Chemistry
Computer Science Applications
Spectroscopy
Molecular Biology
General Medicine
Краткое описание
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme in humans, and a current and promising inhibition target for the development of new chemosensitizing agents due to its ability to remove DNA damage caused by topoisomerase 1 (Top1) poisons such as topotecan and irinotecan. Herein, we report our work on the synthesis and characterization of new Tdp1 inhibitors that combine the arylcoumarin (neoflavonoid) and monoterpenoid moieties. Our results showed that they are potent Tdp1 inhibitors with IC50 values in the submicromolar range. In vivo experiments with mice revealed that compound 3ba (IC50 0.62 µM) induced a significant increase in the antitumor effect of topotecan on the Krebs-2 ascites tumor model. Our results further strengthen the argument that Tdp1 is a druggable target with the potential to be developed into a clinically-potent adjunct therapy in conjunction with Top1 poisons.
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Khomenko T. M. et al. Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy // International Journal of Molecular Sciences. 2019. Vol. 21. No. 1. p. 126.
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Khomenko T. M., Zakharenko A. L., Chepanova A. A., Ilina E. S., Zakharova O. D., Kaledin V. I., Nikolin V. P., Popova N. A., Korchagina D. V., Reynisson J., Chand R., Ayine Tora D. M., Patel J., Leung I. K. H., Volcho K. P., Salakhutdinov N. F., Lavrik O. Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy // International Journal of Molecular Sciences. 2019. Vol. 21. No. 1. p. 126.
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TY - JOUR
DO - 10.3390/ijms21010126
UR - https://doi.org/10.3390/ijms21010126
TI - Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy
T2 - International Journal of Molecular Sciences
AU - Khomenko, Tatyana M
AU - Zakharenko, Alexandra L.
AU - Chepanova, Arina A.
AU - Ilina, Ekaterina S.
AU - Zakharova, Olga D.
AU - Kaledin, Vasily I
AU - Nikolin, Valeriy P.
AU - Popova, Nelly A.
AU - Korchagina, Dina V.
AU - Reynisson, Jóhannes
AU - Chand, Raina
AU - Ayine Tora, Daniel M
AU - Patel, Jinal
AU - Leung, Ivanhoe K. H.
AU - Volcho, Konstantin P.
AU - Salakhutdinov, Nariman F.
AU - Lavrik, Olga I.
PY - 2019
DA - 2019/12/23
PB - MDPI
SP - 126
IS - 1
VL - 21
PMID - 31878088
SN - 1661-6596
SN - 1422-0067
ER -
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@article{2019_Khomenko,
author = {Tatyana M Khomenko and Alexandra L. Zakharenko and Arina A. Chepanova and Ekaterina S. Ilina and Olga D. Zakharova and Vasily I Kaledin and Valeriy P. Nikolin and Nelly A. Popova and Dina V. Korchagina and Jóhannes Reynisson and Raina Chand and Daniel M Ayine Tora and Jinal Patel and Ivanhoe K. H. Leung and Konstantin P. Volcho and Nariman F. Salakhutdinov and Olga I. Lavrik},
title = {Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy},
journal = {International Journal of Molecular Sciences},
year = {2019},
volume = {21},
publisher = {MDPI},
month = {dec},
url = {https://doi.org/10.3390/ijms21010126},
number = {1},
pages = {126},
doi = {10.3390/ijms21010126}
}
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Khomenko, Tatyana M., et al. “Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy.” International Journal of Molecular Sciences, vol. 21, no. 1, Dec. 2019, p. 126. https://doi.org/10.3390/ijms21010126.
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