Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Inhibition of tyrosyl-DNA phosphodiesterase 1 by lipophilic pyrimidine nucleosides. / Zakharenko, Alexandra L.; Drenichev, Mikhail S.; Dyrkheeva, Nadezhda S. и др.
в: Molecules, Том 25, № 16, 3694, 13.08.2020.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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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.
N1 - Publisher Copyright: © 2020 by the authors. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
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