Standard

Promising new inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 4- arylcoumarin and monoterpenoid moieties as components of complex antitumor therapy. / Khomenko, Tatyana M.; Zakharenko, Alexandra L.; Chepanova, Arina A. et al.

In: International Journal of Molecular Sciences, Vol. 21, No. 1, 126, 01.01.2020.

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

Harvard

Khomenko, TM, Zakharenko, AL, Chepanova, AA, Ilina, ES, Zakharova, OD, Kaledin, VI, Nikolin, VP, Popova, NA, Korchagina, DV, Reynisson, J, Chand, R, Ayine-tora, DM, Patel, J, Leung, IKH, Volcho, KP, Salakhutdinov, NF & Lavrik, OI 2020, '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, 126. https://doi.org/10.3390/ijms21010126

APA

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. I. (2020). 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, 21(1), [126]. https://doi.org/10.3390/ijms21010126

Vancouver

Khomenko TM, Zakharenko AL, Chepanova AA, Ilina ES, Zakharova OD, Kaledin VI 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. 2020 Jan 1;21(1):126. doi: 10.3390/ijms21010126

Author

Khomenko, Tatyana M. ; Zakharenko, Alexandra L. ; Chepanova, Arina A. et al. / Promising new inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 4- arylcoumarin and monoterpenoid moieties as components of complex antitumor therapy. In: International Journal of Molecular Sciences. 2020 ; Vol. 21, No. 1.

BibTeX

@article{d041103d40094fc9a0db38b4b43594ad,
title = "Promising new inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 4- arylcoumarin and monoterpenoid moieties as components of complex antitumor therapy",
abstract = "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.",
keywords = "Cancer, Chemical space, Coumarin, DNA repair enzymes, Molecular modeling, Neoflavone, Tdp1 inhibitor, Topoisomerase 1 inhibitors, Topotecan, Tumor, EMPIRICAL SCORING FUNCTIONS, TOPOISOMERASE-I, BIOLOGICAL EVALUATION, chemical space, topotecan, CONSTITUENTS, coumarin, IDENTIFICATION, ENHANCE, neoflavone, molecular modeling, tumor, PROTEIN-LIGAND DOCKING, topoisomerase 1 inhibitors, RHABDOMYOSARCOMA, IRINOTECAN, cancer, COUMARIN DERIVATIVES",
author = "Khomenko, {Tatyana M.} and Zakharenko, {Alexandra L.} and Chepanova, {Arina A.} and Ilina, {Ekaterina S.} and Zakharova, {Olga D.} and Kaledin, {Vasily I.} and Nikolin, {Valeriy P.} and Popova, {Nelly A.} and Korchagina, {Dina V.} and J{\'o}hannes Reynisson and Raina Chand and Ayine-tora, {Daniel M.} and Jinal Patel and Leung, {Ivanhoe K.H.} and Volcho, {Konstantin P.} and Salakhutdinov, {Nariman F.} and Lavrik, {Olga I.}",
note = "Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = jan,
day = "1",
doi = "10.3390/ijms21010126",
language = "English",
volume = "21",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",

}

RIS

TY - JOUR

T1 - Promising new inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 4- arylcoumarin and monoterpenoid moieties as components of complex antitumor therapy

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.

N1 - Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

KW - Cancer

KW - Chemical space

KW - Coumarin

KW - DNA repair enzymes

KW - Molecular modeling

KW - Neoflavone

KW - Tdp1 inhibitor

KW - Topoisomerase 1 inhibitors

KW - Topotecan

KW - Tumor

KW - EMPIRICAL SCORING FUNCTIONS

KW - TOPOISOMERASE-I

KW - BIOLOGICAL EVALUATION

KW - chemical space

KW - topotecan

KW - CONSTITUENTS

KW - coumarin

KW - IDENTIFICATION

KW - ENHANCE

KW - neoflavone

KW - molecular modeling

KW - tumor

KW - PROTEIN-LIGAND DOCKING

KW - topoisomerase 1 inhibitors

KW - RHABDOMYOSARCOMA

KW - IRINOTECAN

KW - cancer

KW - COUMARIN DERIVATIVES

UR - http://www.scopus.com/inward/record.url?scp=85077279055&partnerID=8YFLogxK

U2 - 10.3390/ijms21010126

DO - 10.3390/ijms21010126

M3 - Article

C2 - 31878088

AN - SCOPUS:85077279055

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

M1 - 126

ER -

ID: 22997516