Monoterpene substituted thiazolidin-4-ones as novel TDP1 inhibitors: Synthesis, biological evaluation and docking Full article
Journal |
Bioorganic and Medicinal Chemistry Letters
ISSN: 0960-894X |
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Output data | Year: 2022, Volume: 73, Article number : 128909, Pages count : DOI: 10.1016/j.bmcl.2022.128909 | ||||||
Tags | Monoterpenic derivatives; TDP1 inhibitors; Thiazolidin-4-ones; Tyrosyl-DNA phosphodiesterase 1 | ||||||
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Abstract:
Tyrosyl-DNA phosphodiesterase 1(TDP1) is a promising target for a new therapy in oncological disease as an adjunct to topoisomerase 1 (TOP1) drugs. In this paper, novel thiazolidin-4-one derivatives with a benzyl and monoterpene substituents were synthesized. Compounds with a monoterpene fragment attached via a phenyloxy linker were active against TDP1 with IC50 values in the 1 ÷ 3 μM range, while direct attachment of monoterpene moiety to the thiazolidin-4-one fragment had no activity. Molecular modelling predicted two plausible binding modes of the active compounds both effectively blocking access to the catalytic site of TDP. At non-toxic concentrations the active ligands potentiated the efficacy of the TOP1 poison topotecan in human cervical cancer HeLa cells, but not in non-cancerous HEK293A cells. © 2022 Elsevier Ltd
Cite:
Ivankin D.I.
, Dyrkheeva N.S.
, Zakharenko A.L.
, Ilina E.S.
, Zarkov T.O.
, Reynisson J.
, Luzina O.A.
, Volcho K.P.
, Salakhutdinov N.F.
, Lavrik O.I.
Monoterpene substituted thiazolidin-4-ones as novel TDP1 inhibitors: Synthesis, biological evaluation and docking
Bioorganic and Medicinal Chemistry Letters. 2022. V.73. 128909 . DOI: 10.1016/j.bmcl.2022.128909 WOS Scopus
Monoterpene substituted thiazolidin-4-ones as novel TDP1 inhibitors: Synthesis, biological evaluation and docking
Bioorganic and Medicinal Chemistry Letters. 2022. V.73. 128909 . DOI: 10.1016/j.bmcl.2022.128909 WOS Scopus
Dates:
Published print: | Oct 1, 2022 |
Identifiers:
Web of science | WOS:000863225800005 |
Scopus | 2-s2.0-85135298122 |
OpenAlex | W4288056547 |