Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides

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Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides. / Zakharenko, Alexandra L.; Drenichev, Mikhail S.; Dyrkheeva, Nadezhda S. et al.

In: Molecules, Vol. 25, No. 16, 3694, 13.08.2020.

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

Harvard

Zakharenko, AL, Drenichev, MS, Dyrkheeva, NS, Ivanov, GA, Oslovsky, VE, Ilina, ES, Chernyshova, IA, Lavrik, OI & Mikhailov, SN 2020, 'Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides', Molecules, vol. 25, no. 16, 3694. https://doi.org/10.3390/molecules25163694

APA

Zakharenko, A. L., Drenichev, M. S., Dyrkheeva, N. S., Ivanov, G. A., Oslovsky, V. E., Ilina, E. S., Chernyshova, I. A., Lavrik, O. I., & Mikhailov, S. N. (2020). Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides. Molecules, 25(16), [3694]. https://doi.org/10.3390/molecules25163694

Vancouver

Zakharenko AL, Drenichev MS, Dyrkheeva NS, Ivanov GA, Oslovsky VE, Ilina ES et al. Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides. Molecules. 2020 Aug 13;25(16):3694. doi: 10.3390/molecules25163694

Author

Zakharenko, Alexandra L. ; Drenichev, Mikhail S. ; Dyrkheeva, Nadezhda S. et al. / Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides. In: Molecules. 2020 ; Vol. 25, No. 16.

BibTeX

@article{3e3992738ba7447f88e82361e00c7ef9,

title = "Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides",

abstract = "Inhibition of DNA repair enzymes tyrosyl-DNA phosphodiesterase 1 and poly(ADP-ribose) polymerases 1 and 2 in the presence of pyrimidine nucleoside derivatives was studied here. New effective Tdp1 inhibitors were found in a series of nucleoside derivatives possessing 2′,3′,5′-tri-O-benzoyl-d-ribofuranose and 5-substituted uracil moieties and have half-maximal inhibitory concentrations (IC50) in the lower micromolar and submicromolar range. 2′,3′,5′-Tri-Obenzoyl- 5-iodouridinemanifested the strongest inhibitory effect on Tdp1 (IC50 = 0.6 μM). Adecrease in the number of benzoic acid residues led to a marked decline in the inhibitory activity, and pyrimidine nucleosides lacking lipophilic groups (uridine, 5-fluorouridine, 5-chlorouridine, 5-bromouridine, 5-iodouridine, and ribothymidine) did not cause noticeable inhibition of Tdp1 (IC50 > 50 μM). No PARP1/2 inhibitors were found among the studied compounds (residual activity in the presence of 1mMsubstances was 50-100%). Several O-benzoylated uridine and cytidine derivatives strengthened the action of topotecan on HeLa cervical cancer cells. ",

keywords = "DNA repair, Nucleosides, Tdp1 inhibition, Topotecan, Tyrosyl-DNA phosphodiesterase, PATHWAYS, POLY(ADP-RIBOSE), POLYMERASE, TOPOISOMERASE-I, nucleosides, tyrosyl-DNA phosphodiesterase, DAMAGE RESPONSE, REPAIR, CAMPTOTHECIN, TDP1, DERIVATIVES, topotecan, COVALENT COMPLEXES",

author = "Zakharenko, {Alexandra L.} and Drenichev, {Mikhail S.} and Dyrkheeva, {Nadezhda S.} and Ivanov, {Georgy A.} and Oslovsky, {Vladimir E.} and Ilina, {Ekaterina S.} and Chernyshova, {Irina A.} and Lavrik, {Olga I.} and Mikhailov, {Sergey N.}",

year = "2020",

month = aug,

day = "13",

doi = "10.3390/molecules25163694",

language = "English",

volume = "25",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "16",

}

RIS

TY - JOUR

T1 - Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides

AU - Zakharenko, Alexandra L.

AU - Drenichev, Mikhail S.

AU - Dyrkheeva, Nadezhda S.

AU - Ivanov, Georgy A.

AU - Oslovsky, Vladimir E.

AU - Ilina, Ekaterina S.

AU - Chernyshova, Irina A.

AU - Lavrik, Olga I.

AU - Mikhailov, Sergey N.

PY - 2020/8/13

Y1 - 2020/8/13

N2 - Inhibition of DNA repair enzymes tyrosyl-DNA phosphodiesterase 1 and poly(ADP-ribose) polymerases 1 and 2 in the presence of pyrimidine nucleoside derivatives was studied here. New effective Tdp1 inhibitors were found in a series of nucleoside derivatives possessing 2′,3′,5′-tri-O-benzoyl-d-ribofuranose and 5-substituted uracil moieties and have half-maximal inhibitory concentrations (IC50) in the lower micromolar and submicromolar range. 2′,3′,5′-Tri-Obenzoyl- 5-iodouridinemanifested the strongest inhibitory effect on Tdp1 (IC50 = 0.6 μM). Adecrease in the number of benzoic acid residues led to a marked decline in the inhibitory activity, and pyrimidine nucleosides lacking lipophilic groups (uridine, 5-fluorouridine, 5-chlorouridine, 5-bromouridine, 5-iodouridine, and ribothymidine) did not cause noticeable inhibition of Tdp1 (IC50 > 50 μM). No PARP1/2 inhibitors were found among the studied compounds (residual activity in the presence of 1mMsubstances was 50-100%). Several O-benzoylated uridine and cytidine derivatives strengthened the action of topotecan on HeLa cervical cancer cells.

AB - Inhibition of DNA repair enzymes tyrosyl-DNA phosphodiesterase 1 and poly(ADP-ribose) polymerases 1 and 2 in the presence of pyrimidine nucleoside derivatives was studied here. New effective Tdp1 inhibitors were found in a series of nucleoside derivatives possessing 2′,3′,5′-tri-O-benzoyl-d-ribofuranose and 5-substituted uracil moieties and have half-maximal inhibitory concentrations (IC50) in the lower micromolar and submicromolar range. 2′,3′,5′-Tri-Obenzoyl- 5-iodouridinemanifested the strongest inhibitory effect on Tdp1 (IC50 = 0.6 μM). Adecrease in the number of benzoic acid residues led to a marked decline in the inhibitory activity, and pyrimidine nucleosides lacking lipophilic groups (uridine, 5-fluorouridine, 5-chlorouridine, 5-bromouridine, 5-iodouridine, and ribothymidine) did not cause noticeable inhibition of Tdp1 (IC50 > 50 μM). No PARP1/2 inhibitors were found among the studied compounds (residual activity in the presence of 1mMsubstances was 50-100%). Several O-benzoylated uridine and cytidine derivatives strengthened the action of topotecan on HeLa cervical cancer cells.

KW - DNA repair

KW - Nucleosides

KW - Tdp1 inhibition

KW - Topotecan

KW - Tyrosyl-DNA phosphodiesterase

KW - PATHWAYS

KW - POLY(ADP-RIBOSE)

KW - POLYMERASE

KW - TOPOISOMERASE-I

KW - nucleosides

KW - tyrosyl-DNA phosphodiesterase

KW - DAMAGE RESPONSE

KW - REPAIR

KW - CAMPTOTHECIN

KW - TDP1

KW - DERIVATIVES

KW - topotecan

KW - COVALENT COMPLEXES

UR - http://www.scopus.com/inward/record.url?scp=85089800712&partnerID=8YFLogxK

U2 - 10.3390/molecules25163694

DO - 10.3390/molecules25163694

M3 - Article

C2 - 32823658

AN - SCOPUS:85089800712

VL - 25

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 16

M1 - 3694

ER -

ID: 25290687