Johannes Reynisson j.reynisson@keele.ac.uk
Novel TDP1 Inhibitors: Disubstituted Thiazolidine-2,4-Diones Containing Monoterpene Moieties.
Reynisson, Johannes
Authors
Abstract
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.
| Acceptance Date | Feb 10, 2023 |
|---|---|
| Publication Date | Feb 14, 2023 |
| Journal | International Journal of Molecular Sciences |
| Print ISSN | 1661-6596 |
| Publisher | MDPI |
| DOI | https://doi.org/10.3390/ijms24043834 |
| Keywords | tyrosyl-DNA-phosphodiesterase 1; TDP1 inhibitors; thiazolidine-2,4-dione derivatives |
| Publisher URL | https://www.mdpi.com/1422-0067/24/4/3834 |
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