Novel TDP1 Inhibitors: Disubstituted Thiazolidine-2,4-Diones Containing Monoterpene Moieties.

Autor: Ivankin DI; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Science, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Kornienko TE; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Science, 8, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Mikhailova MA; Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia., Dyrkheeva NS; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Science, 8, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Zakharenko AL; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Science, 8, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Achara C; School of Pharmacy and Bioengineering, Keele University, Hornbeam Building, Newcastle-under-Lyme, Staffordshire ST5 5BC, UK., Reynisson J; School of Pharmacy and Bioengineering, Keele University, Hornbeam Building, Newcastle-under-Lyme, Staffordshire ST5 5BC, UK., Golyshev VM; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Science, 8, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Luzina OA; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Science, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Volcho KP; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Science, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia., Salakhutdinov NF; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Science, 9, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia.; Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia., Lavrik OI; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Science, 8, Akademika Lavrentieva Ave., 630090 Novosibirsk, Russia.; Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Feb 14; Vol. 24 (4). Date of Electronic Publication: 2023 Feb 14.
DOI: 10.3390/ijms24043834
Abstrakt: 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 IC 50 values less than 5 μM. Interestingly, compounds 20d and 21d were the most active, with IC 50 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.
Databáze: MEDLINE
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