El-Sayed Magda A-A, El-Husseiny Walaa M, Abdel-Aziz Naglaa I, El-Azab Adel S, Abuelizz Hatem A, Abdel-Aziz Alaa A-M
a Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy , Mansoura University , Mansoura , Egypt.
b Department of pharmaceutical chemistry, Faculty of pharmacy , Horus university , New Damietta , Egypt.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):199-209. doi: 10.1080/14756366.2017.1407926.
A new series of 4,6-disubstituted 2-(4-(dimethylamino)styryl)quinoline 4a,b-9a,b was synthesized by the reaction of 2-(4-(dimethylamino)styryl)-6-substituted quinoline-4-carboxylic acids 3a,b with thiosemicarbazide, p-hydroxybenzaldehyde, ethylcyanoacetate, and 2,4-pentandione. In addition, the antitumour activity of all synthesized compounds 3a,b-9a,b was studied via MTT assay against two cancer cell lines (HepG2 and HCT116). Furthermore, epidermal growth factor receptor (EGFR) inhibition, using the most potent antitumour compounds, 3a, 3b, 4a, 4b, and 8a, was evaluated. The interpretation of the results showed clearly that the derivatives 3a, 4a, and 4b exhibited the highest antitumour activities against the tested cell lines HepG2 and HCT116 with IC range of 7.7-14.2 µg/ml, in comparison with the reference drugs 5-fluorouracil (IC = 7.9 and 5.3 µg/ml, respectively) and afatinib (IC = 5.4 and 11.4 µg/ml, respectively). In vitro EGFR screening showed that compounds 3a, 3b, 4a, 4b, and 8a exhibited moderate inhibition towards EGFR with IC values at micromolar levels (IC range of 16.01-1.11 µM) compared with the reference drugs sorafenib (IC = 1.14 µM) and erlotinib (IC = 0.1 µM). Molecular docking was performed to study the mode of interaction of compounds 3a and 4b with EGFR kinase.
通过2-(4-(二甲氨基)苯乙烯基)-6-取代喹啉-4-羧酸3a,b与氨基硫脲、对羟基苯甲醛、氰基乙酸乙酯和2,4-戊二酮反应，合成了一系列新的4,6-二取代2-(4-(二甲氨基)苯乙烯基)喹啉4a,b - 9a,b。此外，通过MTT法研究了所有合成化合物3a,b - 9a,b对两种癌细胞系（HepG2和HCT116）的抗肿瘤活性。此外，使用最有效的抗肿瘤化合物3a、3b、4a、4b和8a评估了表皮生长因子受体（EGFR）抑制作用。结果解释清楚地表明，与参考药物5-氟尿嘧啶（IC分别为7.9和5.3μg/ml）和阿法替尼（IC分别为5.4和11.4μg/ml）相比，衍生物3a、4a和4b对测试的癌细胞系HepG2和HCT116表现出最高的抗肿瘤活性，IC范围为7.7 - 14.2μg/ml。体外EGFR筛选表明，与参考药物索拉非尼（IC = 1.14μM）和厄洛替尼（IC = 0.1μM）相比，化合物3a、3b、4a、4b和8a对EGFR表现出中等抑制作用，IC值处于微摩尔水平（IC范围为16.01 - 1.11μM）。进行了分子对接以研究化合物3a和4b与EGFR激酶的相互作用模式。
