Research output: Contribution to journal › Article › peer-review
Effective Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 Based on Monoterpenoids as Potential Agents for Antitumor Therapy. / Chepanova, A. A.; Li-Zhulanov, N. S.; Sukhikh, A. S. et al.
In: Russian Journal of Bioorganic Chemistry, Vol. 45, No. 6, 01.11.2019, p. 647-655.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Effective Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 Based on Monoterpenoids as Potential Agents for Antitumor Therapy
AU - Chepanova, A. A.
AU - Li-Zhulanov, N. S.
AU - Sukhikh, A. S.
AU - Zafar, A.
AU - Reynisson, J.
AU - Zakharenko, A. L.
AU - Zakharova, O. D.
AU - Korchagina, D. V.
AU - Volcho, K. P.
AU - Salakhutdinov, N. F.
AU - Lavrik, O. I.
N1 - Publisher Copyright: © 2019, Pleiades Publishing, Ltd.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the important DNA repair enzymes responsible for the repair of DNA damage caused by anticancer drugs, such as topotecan. In this regard, enzyme activity is one of the possible causes of tumor resistance to chemotherapy, and the use of inhibitors of this enzyme is considered as a promising adjuvant therapy. We have obtained a number of new isomeric naphthyl derivatives of thiophenyl octahydro-2H-chromene, the structure of one of which is confirmed by X-ray structural analysis. Based on molecular modeling data, the structure of the ligand-Tdp1 complex has been proposed. All compounds obtained inhibit Tdp1 at a concentration of about 2 μM. Low toxicity of three compounds was shown, which makes them promising candidates for the development of accompanying cancer therapy.
AB - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the important DNA repair enzymes responsible for the repair of DNA damage caused by anticancer drugs, such as topotecan. In this regard, enzyme activity is one of the possible causes of tumor resistance to chemotherapy, and the use of inhibitors of this enzyme is considered as a promising adjuvant therapy. We have obtained a number of new isomeric naphthyl derivatives of thiophenyl octahydro-2H-chromene, the structure of one of which is confirmed by X-ray structural analysis. Based on molecular modeling data, the structure of the ligand-Tdp1 complex has been proposed. All compounds obtained inhibit Tdp1 at a concentration of about 2 μM. Low toxicity of three compounds was shown, which makes them promising candidates for the development of accompanying cancer therapy.
KW - cytotoxicity
KW - octahydro-2H-chromene
KW - topotecan
KW - tyrosyl-DNA phosphodiesterase 1 inhibitors
KW - ASSAY
KW - EMPIRICAL SCORING FUNCTIONS
KW - IDENTIFICATION
KW - ENHANCE
KW - PROTEIN-LIGAND DOCKING
KW - TDP1
KW - IN-VIVO
KW - BIOLOGICAL EVALUATION
KW - BINDING
UR - http://www.scopus.com/inward/record.url?scp=85077900104&partnerID=8YFLogxK
U2 - 10.1134/S1068162019060104
DO - 10.1134/S1068162019060104
M3 - Article
AN - SCOPUS:85077900104
VL - 45
SP - 647
EP - 655
JO - Russian Journal of Bioorganic Chemistry
JF - Russian Journal of Bioorganic Chemistry
SN - 1068-1620
IS - 6
ER -
ID: 23144772