Standard

A novel class of tyrosyl-DNA phosphodiesterase 1 inhibitors that contains the octahydro-2H-chromen-4-ol scaffold. / Li-Zhulanov, Nikolai S.; Zakharenko, Alexandra L.; Chepanova, Arina A. et al.

In: Molecules, Vol. 23, No. 10, 2468, 26.09.2018.

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

Harvard

Li-Zhulanov, NS, Zakharenko, AL, Chepanova, AA, Patel, J, Zafar, A, Volcho, KP, Salakhutdinov, NF, Reynisson, J, Leung, IKH & Lavrik, OI 2018, 'A novel class of tyrosyl-DNA phosphodiesterase 1 inhibitors that contains the octahydro-2H-chromen-4-ol scaffold', Molecules, vol. 23, no. 10, 2468. https://doi.org/10.3390/molecules23102468

APA

Li-Zhulanov, N. S., Zakharenko, A. L., Chepanova, A. A., Patel, J., Zafar, A., Volcho, K. P., Salakhutdinov, N. F., Reynisson, J., Leung, I. K. H., & Lavrik, O. I. (2018). A novel class of tyrosyl-DNA phosphodiesterase 1 inhibitors that contains the octahydro-2H-chromen-4-ol scaffold. Molecules, 23(10), [2468]. https://doi.org/10.3390/molecules23102468

Vancouver

Li-Zhulanov NS, Zakharenko AL, Chepanova AA, Patel J, Zafar A, Volcho KP et al. A novel class of tyrosyl-DNA phosphodiesterase 1 inhibitors that contains the octahydro-2H-chromen-4-ol scaffold. Molecules. 2018 Sept 26;23(10):2468. doi: 10.3390/molecules23102468

Author

Li-Zhulanov, Nikolai S. ; Zakharenko, Alexandra L. ; Chepanova, Arina A. et al. / A novel class of tyrosyl-DNA phosphodiesterase 1 inhibitors that contains the octahydro-2H-chromen-4-ol scaffold. In: Molecules. 2018 ; Vol. 23, No. 10.

BibTeX

@article{cab251d7862445be803cd24a1a6afaa1,
title = "A novel class of tyrosyl-DNA phosphodiesterase 1 inhibitors that contains the octahydro-2H-chromen-4-ol scaffold",
abstract = "Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage. Tdp1 is a current inhibition target for the development of improved anticancer treatments, as its inhibition may enhance the therapeutic effect of topoisomerase 1 poisons. Here, we report a study on the development of a novel class of Tdp1 inhibitors that is based on the octahydro-2H-chromene scaffold. Inhibition and binding assays revealed that these compounds are potent inhibitors of Tdp1, with IC50 and KD values in the low micromolar concentration range. Molecular modelling predicted plausible conformations of the active ligands, blocking access to the enzymatic machinery of Tdp1. Our results thus help establish a structural-activity relationship for octahydro-2H-chromene-based Tdp1 inhibitors, which will be useful for future Tdp1 inhibitor development work.",
keywords = "Anticancer agent, Biochemical assay, Chemical space, DNA repair enzyme, Molecular modeling, Structural-activity relationships, Synthesis, Tdp1 inhibitor, synthesis, structural-activity relationships, ISOPULEGOL, ANALGESIC ACTIVITY, anticancer agent, molecular modeling, biochemical assay, TDP1, BIOLOGICAL EVALUATION, chemical space",
author = "Li-Zhulanov, {Nikolai S.} and Zakharenko, {Alexandra L.} and Chepanova, {Arina A.} and Jinal Patel and Ayesha Zafar and Volcho, {Konstantin P.} and Salakhutdinov, {Nariman F.} and J{\'o}hannes Reynisson and Leung, {Ivanhoe K.H.} and Lavrik, {Olga I.}",
note = "Publisher Copyright: {\textcopyright} 2018 by the authors.",
year = "2018",
month = sep,
day = "26",
doi = "10.3390/molecules23102468",
language = "English",
volume = "23",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",

}

RIS

TY - JOUR

T1 - A novel class of tyrosyl-DNA phosphodiesterase 1 inhibitors that contains the octahydro-2H-chromen-4-ol scaffold

AU - Li-Zhulanov, Nikolai S.

AU - Zakharenko, Alexandra L.

AU - Chepanova, Arina A.

AU - Patel, Jinal

AU - Zafar, Ayesha

AU - Volcho, Konstantin P.

AU - Salakhutdinov, Nariman F.

AU - Reynisson, Jóhannes

AU - Leung, Ivanhoe K.H.

AU - Lavrik, Olga I.

N1 - Publisher Copyright: © 2018 by the authors.

PY - 2018/9/26

Y1 - 2018/9/26

N2 - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage. Tdp1 is a current inhibition target for the development of improved anticancer treatments, as its inhibition may enhance the therapeutic effect of topoisomerase 1 poisons. Here, we report a study on the development of a novel class of Tdp1 inhibitors that is based on the octahydro-2H-chromene scaffold. Inhibition and binding assays revealed that these compounds are potent inhibitors of Tdp1, with IC50 and KD values in the low micromolar concentration range. Molecular modelling predicted plausible conformations of the active ligands, blocking access to the enzymatic machinery of Tdp1. Our results thus help establish a structural-activity relationship for octahydro-2H-chromene-based Tdp1 inhibitors, which will be useful for future Tdp1 inhibitor development work.

AB - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage. Tdp1 is a current inhibition target for the development of improved anticancer treatments, as its inhibition may enhance the therapeutic effect of topoisomerase 1 poisons. Here, we report a study on the development of a novel class of Tdp1 inhibitors that is based on the octahydro-2H-chromene scaffold. Inhibition and binding assays revealed that these compounds are potent inhibitors of Tdp1, with IC50 and KD values in the low micromolar concentration range. Molecular modelling predicted plausible conformations of the active ligands, blocking access to the enzymatic machinery of Tdp1. Our results thus help establish a structural-activity relationship for octahydro-2H-chromene-based Tdp1 inhibitors, which will be useful for future Tdp1 inhibitor development work.

KW - Anticancer agent

KW - Biochemical assay

KW - Chemical space

KW - DNA repair enzyme

KW - Molecular modeling

KW - Structural-activity relationships

KW - Synthesis

KW - Tdp1 inhibitor

KW - synthesis

KW - structural-activity relationships

KW - ISOPULEGOL

KW - ANALGESIC ACTIVITY

KW - anticancer agent

KW - molecular modeling

KW - biochemical assay

KW - TDP1

KW - BIOLOGICAL EVALUATION

KW - chemical space

UR - http://www.scopus.com/inward/record.url?scp=85054090656&partnerID=8YFLogxK

U2 - 10.3390/molecules23102468

DO - 10.3390/molecules23102468

M3 - Article

C2 - 30261631

AN - SCOPUS:85054090656

VL - 23

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 10

M1 - 2468

ER -

ID: 16947686