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New hydrazinothiazole derivatives of usnic acid as potent TDP1 inhibitors. / Filimonov, Aleksander S.; Chepanova, Arina A.; Luzina, Olga A. et al.

In: Molecules, Vol. 24, No. 20, 3711, 15.10.2019.

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

Harvard

Filimonov, AS, Chepanova, AA, Luzina, OA, Zakharenko, AL, Zakharova, OD, Ilina, ES, Dyrkheeva, NS, Kuprushkin, MS, Kolotaev, AV, Khachatryan, DS, Patel, J, Leung, IKH, Chand, R, Ayine-Tora, DM, Reynisson, J, Volcho, KP, Salakhutdinov, NF & Lavrik, OI 2019, 'New hydrazinothiazole derivatives of usnic acid as potent TDP1 inhibitors', Molecules, vol. 24, no. 20, 3711. https://doi.org/10.3390/molecules24203711

APA

Filimonov, A. S., Chepanova, A. A., Luzina, O. A., Zakharenko, A. L., Zakharova, O. D., Ilina, E. S., Dyrkheeva, N. S., Kuprushkin, M. S., Kolotaev, A. V., Khachatryan, D. S., Patel, J., Leung, I. K. H., Chand, R., Ayine-Tora, D. M., Reynisson, J., Volcho, K. P., Salakhutdinov, N. F., & Lavrik, O. I. (2019). New hydrazinothiazole derivatives of usnic acid as potent TDP1 inhibitors. Molecules, 24(20), [3711]. https://doi.org/10.3390/molecules24203711

Vancouver

Filimonov AS, Chepanova AA, Luzina OA, Zakharenko AL, Zakharova OD, Ilina ES et al. New hydrazinothiazole derivatives of usnic acid as potent TDP1 inhibitors. Molecules. 2019 Oct 15;24(20):3711. doi: 10.3390/molecules24203711

Author

Filimonov, Aleksander S. ; Chepanova, Arina A. ; Luzina, Olga A. et al. / New hydrazinothiazole derivatives of usnic acid as potent TDP1 inhibitors. In: Molecules. 2019 ; Vol. 24, No. 20.

BibTeX

@article{5884873f2570491bab818cdd454b94a6,
title = "New hydrazinothiazole derivatives of usnic acid as potent TDP1 inhibitors",
abstract = "Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising therapeutic target in cancer therapy. Combination chemotherapy using Tdp1 inhibitors as a component can potentially improve therapeutic response to many chemotherapeutic regimes. A new set of usnic acid derivatives with hydrazonothiazole pharmacophore moieties were synthesized and evaluated as Tdp1 inhibitors. Most of these compounds were found to be potent inhibitors with IC50 values in the low nanomolar range. The activity of the compounds was verified by binding experiments and supported by molecular modeling. The ability of the most effective inhibitors, used at non-toxic concentrations, to sensitize tumors to the anticancer drug topotecan was also demonstrated. The order of administration of the inhibitor and topotecan on their synergistic effect was studied, suggesting that prior or simultaneous introduction of the inhibitor with topotecan is the most effective.",
keywords = "Inhibiting activity, Molecular modeling, Synergetic effect, Topoisomerase 1, Topotecan, Tyrosyl-DNA phosphodiesterase 1 (Tdp1), Usnic acid, TOPOISOMERASES, topoisomerase 1, synergetic effect, COMPLEXES, EMPIRICAL SCORING FUNCTIONS, IDENTIFICATION, usnic acid, inhibiting activity, IN-VITRO, tyrosyl-DNA phosphodiesterase 1 (Tdp1), ANTICANCER, molecular modeling, PROTEIN-LIGAND DOCKING, THIOSEMICARBAZONES, BIOLOGICAL EVALUATION, DNA PHOSPHODIESTERASE 1, topotecan",
author = "Filimonov, {Aleksander S.} and Chepanova, {Arina A.} and Luzina, {Olga A.} and Zakharenko, {Alexandra L.} and Zakharova, {Olga D.} and Ilina, {Ekaterina S.} and Dyrkheeva, {Nadezhda S.} and Kuprushkin, {Maxim S.} and Kolotaev, {Anton V.} and Khachatryan, {Derenik S.} and Jinal Patel and Leung, {Ivanhoe K.H.} and Raina Chand and Ayine-Tora, {Daniel M.} and Johannes Reynisson and Volcho, {Konstantin P.} and Salakhutdinov, {Nariman F.} and Lavrik, {Olga I.}",
note = "Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).",
year = "2019",
month = oct,
day = "15",
doi = "10.3390/molecules24203711",
language = "English",
volume = "24",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "20",

}

RIS

TY - JOUR

T1 - New hydrazinothiazole derivatives of usnic acid as potent TDP1 inhibitors

AU - Filimonov, Aleksander S.

AU - Chepanova, Arina A.

AU - Luzina, Olga A.

AU - Zakharenko, Alexandra L.

AU - Zakharova, Olga D.

AU - Ilina, Ekaterina S.

AU - Dyrkheeva, Nadezhda S.

AU - Kuprushkin, Maxim S.

AU - Kolotaev, Anton V.

AU - Khachatryan, Derenik S.

AU - Patel, Jinal

AU - Leung, Ivanhoe K.H.

AU - Chand, Raina

AU - Ayine-Tora, Daniel M.

AU - Reynisson, Johannes

AU - Volcho, Konstantin P.

AU - Salakhutdinov, Nariman F.

AU - Lavrik, Olga I.

N1 - Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

PY - 2019/10/15

Y1 - 2019/10/15

N2 - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising therapeutic target in cancer therapy. Combination chemotherapy using Tdp1 inhibitors as a component can potentially improve therapeutic response to many chemotherapeutic regimes. A new set of usnic acid derivatives with hydrazonothiazole pharmacophore moieties were synthesized and evaluated as Tdp1 inhibitors. Most of these compounds were found to be potent inhibitors with IC50 values in the low nanomolar range. The activity of the compounds was verified by binding experiments and supported by molecular modeling. The ability of the most effective inhibitors, used at non-toxic concentrations, to sensitize tumors to the anticancer drug topotecan was also demonstrated. The order of administration of the inhibitor and topotecan on their synergistic effect was studied, suggesting that prior or simultaneous introduction of the inhibitor with topotecan is the most effective.

AB - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising therapeutic target in cancer therapy. Combination chemotherapy using Tdp1 inhibitors as a component can potentially improve therapeutic response to many chemotherapeutic regimes. A new set of usnic acid derivatives with hydrazonothiazole pharmacophore moieties were synthesized and evaluated as Tdp1 inhibitors. Most of these compounds were found to be potent inhibitors with IC50 values in the low nanomolar range. The activity of the compounds was verified by binding experiments and supported by molecular modeling. The ability of the most effective inhibitors, used at non-toxic concentrations, to sensitize tumors to the anticancer drug topotecan was also demonstrated. The order of administration of the inhibitor and topotecan on their synergistic effect was studied, suggesting that prior or simultaneous introduction of the inhibitor with topotecan is the most effective.

KW - Inhibiting activity

KW - Molecular modeling

KW - Synergetic effect

KW - Topoisomerase 1

KW - Topotecan

KW - Tyrosyl-DNA phosphodiesterase 1 (Tdp1)

KW - Usnic acid

KW - TOPOISOMERASES

KW - topoisomerase 1

KW - synergetic effect

KW - COMPLEXES

KW - EMPIRICAL SCORING FUNCTIONS

KW - IDENTIFICATION

KW - usnic acid

KW - inhibiting activity

KW - IN-VITRO

KW - tyrosyl-DNA phosphodiesterase 1 (Tdp1)

KW - ANTICANCER

KW - molecular modeling

KW - PROTEIN-LIGAND DOCKING

KW - THIOSEMICARBAZONES

KW - BIOLOGICAL EVALUATION

KW - DNA PHOSPHODIESTERASE 1

KW - topotecan

UR - http://www.scopus.com/inward/record.url?scp=85073476945&partnerID=8YFLogxK

U2 - 10.3390/molecules24203711

DO - 10.3390/molecules24203711

M3 - Article

C2 - 31619021

AN - SCOPUS:85073476945

VL - 24

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 20

M1 - 3711

ER -

ID: 21935525