Ivankin, DI, Kornienko, TE, Mikhailova, MA, Dyrkheeva, NS, Zakharenko, AL, Achara, C, Reynisson, J, Golyshev, VM, Luzina, OA, Volcho, KP, Salakhutdinov, NF and Lavrik, OI (2023) Novel TDP1 Inhibitors: Disubstituted Thiazolidine-2,4-Diones Containing Monoterpene Moieties. International Journal of Molecular Sciences, 24 (4).

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Tyrosyl-DNA-phosphodiesterase 1 (TDP1) is a promising target for antitumor therapy; the use of TDP1 inhibitors with a topoisomerase 1 poison such as topotecan is a potential combination therapy. In this work, a novel series of 3,5-disubstituted thiazolidine-2,4-diones was synthesized and tested against TDP1. The screening revealed some active compounds with IC50 values less than 5 μM. Interestingly, compounds 20d and 21d were the most active, with IC50 values in the submicromolar concentration range. None of the compounds showed cytotoxicity against HCT-116 (colon carcinoma) and MRC-5 (human lung fibroblasts) cell lines in the 1-100 μM concentration range. Finally, this class of compounds did not sensitize cancer cells to the cytotoxic effect of topotecan.

Item Type: Article
Additional Information: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: tyrosyl-DNA-phosphodiesterase 1; TDP1 inhibitors; thiazolidine-2,4-dione derivatives
Subjects: Q Science > QH Natural history
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 03 May 2023 11:41
Last Modified: 03 May 2023 11:41
URI: https://eprints.keele.ac.uk/id/eprint/12546

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