| Autor: |
Zhang, Yadong, Shen, Jiwei, Li, JiaWei, Wang, Zhi, Wang, Yue, Zhu, Yan, Ding, Shi, Zhou, YunPeng, Chen, Ye, Liu, Ju |
| Předmět: |
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| Zdroj: |
New Journal of Chemistry; 12/14/2023, Vol. 47 Issue 46, p21318-21331, 14p |
| Abstrakt: |
Two series of substituted thieno[3,2-d]pyrimidine derivatives as EZH2 inhibitors were synthesized via structural modifications of tazemetostat. The antiproliferative activity of compounds against SU-DHL-6, WSU-DLCL-2, K562, H358 and H1703 cancer cell lines and the toxicity against HEK293T cells were evaluated. The most promising compound 12e had a remarkable antitumor activity against SU-DHL-6, WSU-DLCL-2 and K562 cells (IC50 = 0.55 μM, 0.95 μM and 1.68 μM, respectively) and low toxicity against HEK-293T cells (CC50 = 15.09 μM). The preliminary structure–activity relationship (SAR) studies indicate that piperidine-2,6-dione was more suitable for a P1 moiety and benzyl-linked morpholine for a P5 moiety, which were beneficial for improving the antitumor activities. The biological evaluation showed that 12e can significantly affect lymphoma cell morphology, and induce the apoptosis of SU-DHL-6 cells in a concentration-dependent manner and inhibit their migration. These findings indicated that 12e would be an attractive chemical tool for the further optimization and evaluation of new EZH2 inhibitors. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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