HDAC8型
化学
HDAC6型
对接(动物)
细胞凋亡
HDAC1型
IC50型
半胱氨酸蛋白酶
细胞周期检查点
组蛋白
药理学
细胞培养
细胞周期
半胱氨酸蛋白酶3
组蛋白脱乙酰基酶
生物化学
体外
程序性细胞死亡
生物
DNA
护理部
医学
遗传学
作者
Abdelrahman Hamdi,Walaa M. Elhusseiny,Dina I.A. Othman,Abdullah Haikal,Ahmed H. Bakheit,Adel S. El-Azab,Mohamed H.M. Al-Agamy,Alaa A.-M. Abdel-Aziz
标识
DOI:10.1016/j.ejmech.2022.114827
摘要
The antitumor activity of the newly synthesized 5-arylidenethiazolidine-2,4-dione derivatives 18a-f and 19a-f was investigated, compared to doxorubicin (IC50 = 4.17-8.87 μM) and SAHA (IC50 = 2.70-7.11 μM). Among the tested molecules, compounds 18b, 18c, 18f, 19d, and 19e displayed the highest antitumor activity against cancer cell lines (IC50 = 3.16-28.94 μM). Further, compounds 18b, 18c, 18f, and 19d were tested as Histone deacetylases (HDACs) inhibitors compared with Entinostat (IC50 = 0.093-0.75 μM). Compounds 18b, 18c, 18f, and 19d inhibited HDAC1, HDAC2, HDAC8, and HDAC6 enzymes with IC50 values ranging from 0.144 to 1.741 μM. In addition, compound 18b caused apoptosis via a mitochondrial-mediated pathway and led to cell cycle arrest at the G1 phase. It also increased caspases-3 and caspases-7 by 5.2-3.9 and 9.1-3.7 folds, respectively. The molecular docking analysis of compounds 18b and 18c revealed that they could bind to the active sites of HDAC1, HDAC2, HDAC8, and HDAC6 like co-crystallized inhibitors.
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