Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Novel group of tyrosyl-DNA-phosphodiesterase 1 inhibitors based on disaccharide nucleosides as drug prototypes for anti-cancer therapy. / Komarova, Anastasia O.; Drenichev, Mikhail S.; Dyrkheeva, Nadezhda S. и др.
в: Journal of Enzyme Inhibition and Medicinal Chemistry, Том 33, № 1, 07.09.2018, стр. 1415-1429.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Novel group of tyrosyl-DNA-phosphodiesterase 1 inhibitors based on disaccharide nucleosides as drug prototypes for anti-cancer therapy
AU - Komarova, Anastasia O.
AU - Drenichev, Mikhail S.
AU - Dyrkheeva, Nadezhda S.
AU - Kulikova, Irina V.
AU - Oslovsky, Vladimir E.
AU - Zakharova, Olga D.
AU - Zakharenko, Alexandra L.
AU - Mikhailov, Sergey N.
AU - Lavrik, Olga I.
N1 - Publisher Copyright: © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/9/7
Y1 - 2018/9/7
N2 - A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors based on disaccharide nucleosides was identified. TDP1 plays an essential role in the resistance of cancer cells to currently used antitumour drugs based on Top1 inhibitors such as topotecan and irinotecan. The most effective inhibitors investigated in this study have IC50 values (half-maximal inhibitory concentration) in 0.4–18.5 µM range and demonstrate relatively low own cytotoxicity along with significant synergistic effect in combination with anti-cancer drug topotecan. Moreover, kinetic parameters of the enzymatic reaction and fluorescence anisotropy were measured using different types of DNA-biosensors to give a sufficient insight into the mechanism of inhibitor’s action.
AB - A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors based on disaccharide nucleosides was identified. TDP1 plays an essential role in the resistance of cancer cells to currently used antitumour drugs based on Top1 inhibitors such as topotecan and irinotecan. The most effective inhibitors investigated in this study have IC50 values (half-maximal inhibitory concentration) in 0.4–18.5 µM range and demonstrate relatively low own cytotoxicity along with significant synergistic effect in combination with anti-cancer drug topotecan. Moreover, kinetic parameters of the enzymatic reaction and fluorescence anisotropy were measured using different types of DNA-biosensors to give a sufficient insight into the mechanism of inhibitor’s action.
KW - Disaccharide nucleosides
KW - TDP1 inhibitor
KW - topotecan
KW - tyrosyl-DNA phosphodiesterase 1
KW - Humans
KW - Cells, Cultured
KW - Structure-Activity Relationship
KW - Phosphodiesterase Inhibitors/chemical synthesis
KW - Topotecan/chemical synthesis
KW - Antineoplastic Agents/chemical synthesis
KW - Phosphoric Diester Hydrolases/metabolism
KW - Dose-Response Relationship, Drug
KW - Nucleosides/chemical synthesis
KW - Molecular Structure
KW - Cell Proliferation/drug effects
KW - Disaccharides/chemical synthesis
KW - Drug Screening Assays, Antitumor
KW - POLY(ADP-RIBOSE) POLYMERASE
KW - HUMAN-CELLS
KW - TOPOISOMERASE-I
KW - SPINOCEREBELLAR ATAXIA
KW - DERIVATIVES
KW - REPAIR ENZYME
KW - CRYSTAL-STRUCTURE
KW - DAMAGE
KW - TDP1
KW - PYRIMIDINE NUCLEOSIDES
UR - http://www.scopus.com/inward/record.url?scp=85052929469&partnerID=8YFLogxK
U2 - 10.1080/14756366.2018.1509210
DO - 10.1080/14756366.2018.1509210
M3 - Article
C2 - 30191738
AN - SCOPUS:85052929469
VL - 33
SP - 1415
EP - 1429
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
SN - 1475-6366
IS - 1
ER -
ID: 16484625