Key Laboratory of Original New Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, 110066, PR China.
Eur J Med Chem. 2013 Jun;64:62-73. doi: 10.1016/j.ejmech.2013.04.001. Epub 2013 Apr 15.
A series of novel bisquinoline derivatives connected by a 4-oxy-3-fluoroaniline moiety were synthesized and evaluated for their in vitro antitumour activities against a panel of five cancer cell lines (H460, HT-29, MKN-45, U87MG, and SMMC-7721). Most of compounds tested showed a potent activity and high selectivity towards the H460 and MKN-45 cell lines. Among the compounds tested, six (15d, 15e, 15m, 15n, 16a, and 16i) were further examined for their c-Met kinase activity; the compounds showed high efficacy with IC50 values in the single-digit nM range. An analysis of structure-activity relationships indicated that an unsubstituted or a halogen-substituted phenyl ring on the 2-arylquinoline-4-carboxamide moiety was favourable for antitumour activity.
合成了一系列通过 4-氧基-3-氟苯胺部分连接的新型双喹啉衍生物，并对其进行了体外抗肿瘤活性评估，以筛选针对五种癌细胞系（H460、HT-29、MKN-45、U87MG 和 SMMC-7721）的活性。大多数测试的化合物对 H460 和 MKN-45 细胞系具有很强的活性和高选择性。在测试的化合物中，有六种（15d、15e、15m、15n、16a 和 16i）进一步研究了它们对 c-Met 激酶的活性；这些化合物的疗效很高，IC50 值在十位数 nM 范围内。构效关系分析表明，2-芳基喹啉-4-甲酰胺部分上未取代或卤素取代的苯基环有利于抗肿瘤活性。
