Pharmaceutical Chemistry Department, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Omar Almukhtar University, Libya.
Arch Pharm (Weinheim). 2023 Jul;356(7):e2300137. doi: 10.1002/ardp.202300137. Epub 2023 May 5.
Novel thiazolidine-2,4-diones have been developed and estimated as conjoint inhibitors of EGFR 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 (IC = 15.22, 8.65, and 8.80 µM), A549 (IC = 7.10, 6.55, and 8.11 µM), MCF-7 (IC = 14.56, 6.65, and 7.09 µM) and HepG2 (IC = 11.90, 5.35, and 5.60 µM) mass cell lines, correspondingly. Although compounds 6a, 6b, and 6c disclosed poorer effects than sorafenib (IC = 4.00, 4.04, 5.58, and 5.05 µM) against the tested cell sets, congeners 6b and 6c demonstrated higher actions than erlotinib (IC = 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 IC = 0.85, 0.90, 1.50, and 1.80 µM, respectively. Moreover, compounds 6b, 6a, 6c, and 6i could interfere with the EGFR performing strongest effects with IC = 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.
新型噻唑烷-2,4-二酮类化合物已被开发并评估为 EGFR 和 VEGFR-2 的联合抑制剂，用于抑制 HCT-116、MCF-7、A549 和 HepG2 细胞。化合物 6a、6b 和 6c 被认为是针对 HCT116（IC = 15.22、8.65 和 8.80 µM）、A549（IC = 7.10、6.55 和 8.11 µM）、MCF-7（IC = 14.56、6.65 和 7.09 µM）和 HepG2（IC = 11.90、5.35 和 5.60 µM）细胞系的优势同系物。尽管化合物 6a、6b 和 6c 对测试细胞系的抑制作用不如索拉非尼（IC = 4.00、4.04、5.58 和 5.05 µM），但同系物 6b 和 6c 对 HCT116、MCF-7 和 HepG2 细胞的作用高于厄洛替尼（IC = 7.73、5.49、8.20 和 13.91 µM），而对 A549 细胞的作用则较小。高度有效的衍生物 4e-i 和 6a-c 被检测对 VERO 正常细胞株的影响。发现化合物 6b、6c、6a 和 4i 是最有效的衍生物，它们分别通过 IC = 0.85、0.90、1.50 和 1.80 µM 抑制 VEGFR-2。此外，化合物 6b、6a、6c 和 6i 可以通过 IC = 0.30、0.35、0.50 和 1.00 µM 分别对 EGFR 产生最强的干扰作用。更重要的是，6a、6b 和 6c 在计算机 ADMET 特性预测中表现良好。
