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

Reynisson, Johannes

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.

Citation

Reynisson, J. (2023). Novel TDP1 Inhibitors: Disubstituted Thiazolidine-2,4-Diones Containing Monoterpene Moieties. International Journal of Molecular Sciences, https://doi.org/10.3390/ijms24043834

• 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