已经开发了新型噻唑烷-2,4-二酮,并估计作为EGFRT790M和VEGFR-2对HCT-116,MCF-7,A549和HepG2细胞的联合抑制剂。化合物6a,6b,已知6c是HCT116的优势同源物(IC50=15.22、8.65和8.80µM),A549(IC50=7.10、6.55和8.11µM),MCF-7(IC50=14.56,6.65和7.09µM)和HepG2(IC50=11.90,5.35和5.60µM)质量细胞系,相应地。虽然化合物6a、6b,和6c揭示了比索拉非尼(IC50=4.00,4.04,5.58和5.05µM)对测试细胞组的效果较差,同源物6b和6c对HCT116、MCF-7和HepG2细胞表现出比厄洛替尼更高的作用(IC50=7.73、5.49、8.20和13.91µM),在A549电池上性能较低。与VERO正常细胞株相比,检查了非常有效的衍生物4e-i和6a-c。化合物6b,6c,a.发现4i是最有效的衍生物,其抑制VEGFR-2的IC50=0.85、0.90、1.50和1.80µM,分别。此外,化合物6b,a.6c,和6i可能干扰EGFRT790M,IC50=0.30、0.35、0.50和1.00µM,分别。更重要的是,a.6b,和6c表示令人满意的计算机计算的ADMET曲线。
Novel thiazolidine-2,4-diones have been developed and estimated as conjoint inhibitors of EGFRT790M and VEGFR-2 against HCT-116, MCF-7, A549, and HepG2 cells. Compounds 6a, 6b, and 6c were known to be the dominant advantageous congeners against HCT116 (IC50 = 15.22, 8.65, and 8.80 µM), A549 (IC50 = 7.10, 6.55, and 8.11 µM), MCF-7 (IC50 = 14.56, 6.65, and 7.09 µM) and HepG2 (IC50 = 11.90, 5.35, and 5.60 µM) mass cell lines, correspondingly. Although compounds 6a, 6b, and 6c disclosed poorer effects than sorafenib (IC50 = 4.00, 4.04, 5.58, and 5.05 µM) against the tested cell sets, congeners 6b and 6c demonstrated higher actions than erlotinib (IC50 = 7.73, 5.49, 8.20, and 13.91 µM) against HCT116, MCF-7 and HepG2 cells, yet lesser performance on A549 cells. The hugely effective derivatives 4e-i and 6a-c were inspected versus VERO normal cell strains. Compounds 6b, 6c, 6a, and 4i were found to be the most effective derivatives, which suppressed VEGFR-2 by IC50 = 0.85, 0.90, 1.50, and 1.80 µM, respectively. Moreover, compounds 6b, 6a, 6c, and 6i could interfere with the EGFRT790M performing strongest effects with IC50 = 0.30, 0.35, 0.50, and 1.00 µM, respectively. What is more, 6a, 6b, and 6c represented satisfactory in silico computed ADMET profile.