摘要
目的设计并合成1-苯氨基-5H-哒嗪并[4,5-b]吲哚类化合物,评价其抗肿瘤活性。方法以5-乙酰氧基-6-溴-2-溴甲基-1-环丙基-1H-吲哚-3-羧酸乙酯为起始原料,经多步反应合成目标化合物。采用MTT法,gefitinib为阳性对照药,以Bel-7402和HT-1080为测试细胞株对目标化合物抗肿瘤活性进行进行检测。结果合成了8个未见文献报道的新化合物,其结构经1H-NMR和MS确证。体外活性实验表明:多种化合物显示良好的抗肿瘤活性,其中化合物10f对Bel-7402和HT-1080肿瘤细胞株的抑制作用分别是阳性对照药gefitinib的6倍和7倍。结论1-苯氨基的苯环上的取代基和1-苯氨基-5H-哒嗪并[4,5-b]吲哚的8位引入的3-[[5-(脂肪(环)胺甲基)呋喃-2-基]甲硫基]丙氧基中脂肪(环)氨的种类均显著影响化合物的活性。
Objective To design and synthesize a series of 1-anilino-5H-pyridazino [4,5-b] indole derivatives, and toevaluate their anti-tumor avtivities in vitro. Methods The target compounds were synthesized in several steps starting from ethyl 5-acetoxy-6-bromo-2-bromomethyl-l-cyclopropylindole-3-carboxylate, and their anti-tumor avtivities against cancer cell lines Bel-7402 and HT-1080 were tested by the MTT method in vitro, with gefitinib as the positive control. Results Eight compounds were synthesized and their structures were confirmed by 1H-NMR and MS. Many of this kind of compounds exhibited potent anticancer avtivity, especially compound 10f. conclusion The substitutents on the aniline ring and 5-(alkylaminomethyl) furan-2-ylmethylthiopropoxy side chains at the C-8 position of the 1-anilino-5H pyridazino [4, 5-b] indole have a very important effects on anticancer activities.
出处
《中南药学》
CAS
2008年第2期144-148,共5页
Central South Pharmacy