Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):573-591. doi: 10.1080/14756366.2021.2017911.
Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds , , and showed IC from 17.39 to 47.10 µM against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound which came second with regard to antitumor assay with IC = 24.10, 40.90, and 33.40 µM against aforementioned cell lines, respectively. Furthermore, Compound increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, showed IC of 253 and 381 nM against HER2 and FGFR, respectively.
基于喹唑啉、喹喔啉和硝基苯骨架以及 VEGFR-2 抑制剂的药效团特征，设计并合成了 17 种新型化合物。与索拉非尼的 54.00 nM 相比，新衍生物的 VEGFR-2 IC 值范围为 60.00 至 123.85 nM。化合物 、 和 对人癌细胞系（肝癌细胞系 HepG2、前列腺癌细胞系 PC3 和乳腺癌细胞系 MCF-7）的 IC 值为 17.39 至 47.10 µM。同时，在 VEGFR-2 抑制方面排名第一的化合物 ，在抗肿瘤测定方面排名第二，其 IC 值分别为 24.10、40.90 和 33.40 µM。此外，化合物 使 HepG2 的细胞凋亡率从 1.20%增加到 12.46%，同时使 Caspase-3、BAX 和 P53 的水平分别从 49.6274、40.62 和 42.84 增加到 561.427、395.04 和 415.027 pg/mL。此外，化合物 对 HER2 和 FGFR 的 IC 值分别为 253 和 381 nM。
