The influence of an enamine usnic acid derivative (a tyrosyl-DNA phosphodiesterase 1 inhibitor) on the therapeutic effect of topotecan against transplanted tumors in vivo

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The influence of an enamine usnic acid derivative (a tyrosyl-DNA phosphodiesterase 1 inhibitor) on the therapeutic effect of topotecan against transplanted tumors in vivo. / Nikolin, V. P.; Popova, N. A.; Kaledin, V. I. et al.

In: Clinical and Experimental Metastasis, Vol. 38, No. 5, 10.2021, p. 431-440.

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

BibTeX

@article{7cb7d63c21f5496dbf4f6d5771c590e0,

title = "The influence of an enamine usnic acid derivative (a tyrosyl-DNA phosphodiesterase 1 inhibitor) on the therapeutic effect of topotecan against transplanted tumors in vivo",

abstract = "Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for 3′-end DNA lesions, predominantly stalled DNA–topoisomerase 1 (Top1) cleavage complexes. Tdp1 is a promising target for anticancer therapy based on DNA damage caused by Top1 poisoning. Earlier, we have reported about usnic acid enamine derivatives that are Tdp1 inhibitors sensitizing tumor cells to the action of Top1 poison (Zakharenko in J Nat Prod 79:2961−2967, 2016). In the present work, we showed a sensitizing effect of an enamine derivative of usnic acid (when administered intragastrically) on Lewis lung carcinoma in mice in combination with topotecan (TPT, Top1 poison used in the clinic). In the presence of the usnic acid derivative, both the volume of the primary tumor and the number of metastases significantly diminished. The absence of acute toxicity of this compound was demonstrated, as was the importance of the method of its administration for the manifestation of the sensitizing properties.",

keywords = "DNA repair enzymes, Enamine usnic acid derivative, Lewis lung carcinoma, Tdp1 inhibitor, Topotecan",

author = "Nikolin, {V. P.} and Popova, {N. A.} and Kaledin, {V. I.} and Luzina, {O. A.} and Zakharenko, {A. L.} and Salakhutdinov, {N. F.} and Lavrik, {O. I.}",

note = "Funding Information: This work was funded by a Grant from the Ministry of Science and Higher Education Russian Federation (Agreement No. 075-15-2020-773). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature B.V.",

year = "2021",

month = oct,

doi = "10.1007/s10585-021-10113-y",

language = "English",

volume = "38",

pages = "431--440",

journal = "Clinical and Experimental Metastasis",

issn = "0262-0898",

publisher = "Springer Science and Business Media B.V.",

number = "5",

}

RIS

TY - JOUR

T1 - The influence of an enamine usnic acid derivative (a tyrosyl-DNA phosphodiesterase 1 inhibitor) on the therapeutic effect of topotecan against transplanted tumors in vivo

AU - Nikolin, V. P.

AU - Popova, N. A.

AU - Kaledin, V. I.

AU - Luzina, O. A.

AU - Zakharenko, A. L.

AU - Salakhutdinov, N. F.

AU - Lavrik, O. I.

N1 - Funding Information: This work was funded by a Grant from the Ministry of Science and Higher Education Russian Federation (Agreement No. 075-15-2020-773). Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature B.V.

PY - 2021/10

Y1 - 2021/10

N2 - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for 3′-end DNA lesions, predominantly stalled DNA–topoisomerase 1 (Top1) cleavage complexes. Tdp1 is a promising target for anticancer therapy based on DNA damage caused by Top1 poisoning. Earlier, we have reported about usnic acid enamine derivatives that are Tdp1 inhibitors sensitizing tumor cells to the action of Top1 poison (Zakharenko in J Nat Prod 79:2961−2967, 2016). In the present work, we showed a sensitizing effect of an enamine derivative of usnic acid (when administered intragastrically) on Lewis lung carcinoma in mice in combination with topotecan (TPT, Top1 poison used in the clinic). In the presence of the usnic acid derivative, both the volume of the primary tumor and the number of metastases significantly diminished. The absence of acute toxicity of this compound was demonstrated, as was the importance of the method of its administration for the manifestation of the sensitizing properties.

AB - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for 3′-end DNA lesions, predominantly stalled DNA–topoisomerase 1 (Top1) cleavage complexes. Tdp1 is a promising target for anticancer therapy based on DNA damage caused by Top1 poisoning. Earlier, we have reported about usnic acid enamine derivatives that are Tdp1 inhibitors sensitizing tumor cells to the action of Top1 poison (Zakharenko in J Nat Prod 79:2961−2967, 2016). In the present work, we showed a sensitizing effect of an enamine derivative of usnic acid (when administered intragastrically) on Lewis lung carcinoma in mice in combination with topotecan (TPT, Top1 poison used in the clinic). In the presence of the usnic acid derivative, both the volume of the primary tumor and the number of metastases significantly diminished. The absence of acute toxicity of this compound was demonstrated, as was the importance of the method of its administration for the manifestation of the sensitizing properties.

KW - DNA repair enzymes

KW - Enamine usnic acid derivative

KW - Lewis lung carcinoma

KW - Tdp1 inhibitor

KW - Topotecan

UR - http://www.scopus.com/inward/record.url?scp=85112045171&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/06bf8935-4699-35c5-958a-436d3e1d8e0f/

U2 - 10.1007/s10585-021-10113-y

DO - 10.1007/s10585-021-10113-y

M3 - Article

C2 - 34370156

AN - SCOPUS:85112045171

VL - 38

SP - 431

EP - 440

JO - Clinical and Experimental Metastasis

JF - Clinical and Experimental Metastasis

SN - 0262-0898

IS - 5

ER -

ID: 34145598