TY - JOUR
T1 - Novel TDP1 Inhibitors: Disubstituted Thiazolidine-2,4-Diones Containing Monoterpene Moieties
AU - Ivankin, Dmitry I
AU - Kornienko, Tatyana E
AU - Mikhailova, Marina A
AU - Dyrkheeva, Nadezhda S
AU - Zakharenko, Alexandra L
AU - Achara, Chigozie
AU - Reynisson, Jóhannes
AU - Golyshev, Victor M
AU - Luzina, Olga A
AU - Volcho, Konstantin P
AU - Salakhutdinov, Nariman F
AU - Lavrik, Olga I
N1 - Funding: The research was supported by the Russian Science Foundation (grant 19-13-00040).
PY - 2023/2/14
Y1 - 2023/2/14
N2 - 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.
AB - 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.
KW - TDP1 inhibitors
KW - thiazolidine-2,4-dione derivatives
KW - tyrosyl-DNA-phosphodiesterase 1
UR - https://www.mendeley.com/catalogue/2f18e424-0c1e-3cad-bb69-2b9df0754b2c/
U2 - 10.3390/ijms24043834
DO - 10.3390/ijms24043834
M3 - Article
C2 - 36835244
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 4
M1 - 3834
ER -