Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, October University for Modern Science and Arts (MSA), Cairo 12611, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Molecules. 2019 Mar 25;24(6):1175. doi: 10.3390/molecules24061175.
The quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds , , , and exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound induced a significant disruption in the cell cycle profile and cell cycle arrest at the G2/M phase boundary. In further assays, the cytotoxic effect of the highly active compounds was determined using a normal Caucasian fibroblast-like fetal lung cell line (WI-38). Compound could be considered as a lead compound that merits further optimization and development as an anti-cancer and an apoptotic inducing candidate against the HCT116 cell line.
喹喔啉支架是发现活性化疗药物的有前途的平台。合成了三个系列的喹喔啉衍生物，并对三种肿瘤细胞系（HCT116 人结肠癌细胞、HepG2、肝肝癌细胞和 MCF-7、人乳腺癌腺癌细胞系）进行了生物评价，此外还对 VEGFR-2 酶抑制活性进行了评价。化合物 、 、 、 和 对测试的细胞系表现出有希望的活性，对 VEGFR-2 的活性较弱。化合物 导致细胞周期谱显著中断，并在 G2/M 期边界处发生细胞周期阻滞。在进一步的试验中，使用正常的高加索人成纤维样胎儿肺细胞系（WI-38）测定了高活性化合物的细胞毒性作用。化合物 可以被认为是一个值得进一步优化和开发的先导化合物，作为一种抗癌和诱导凋亡的候选药物，针对 HCT116 细胞系。
