5H-哒嗪并[4,5-b]吲哚类新化合物的合成及抗肿瘤细胞增殖活性

Synthesis and antiproliferative activity of novel 5H-pyridazino[4,5-b]indole derivatives

目的设计并合成5H-哒嗪并[4,5-b]吲哚类化合物,评价其体外抗肿瘤细胞增殖活性。方法以7-溴-1-氯-8-(3-氯丙氧基)-5-环丙基-5H-哒嗪并[4,5-b]吲哚为起始原料,经取代、醚化、Mannich反应、选择性氧化共3步或4步反应合成目标化合物;以吉非替尼(gefitinib)为阳性对照药,采用MTT法测定了目标化合物对肿瘤细胞株Bel-7402和HT-1080的抗增殖活性。结果与结论合成了13个化合物,其中12个是未见文献报道的新化合物,其结构经1H-NMR、MS谱确证;8个化合物显示出较好的抗肿瘤细胞增殖活性,其中,化合物4a和5a抗增殖活性突出,分别为吉非替尼的3倍和4倍。

Aim To design and synthesize 5H-pyridazino[4,5-b]indole derivatives and evaluate their in vitro antiproliferative activities.Methods The target compounds were synthesized in 3-4 steps including substitution reaction,etherification,Mannich reaction and selective oxidation starting from 7-bromo-1-chloro-8-（3-chloropropoxy）-5-cyclopropyl-5H-pyridazino[4,5-b]indole,and their antiproliferative activities against cancer cell lines,Bel-7402 and HT-1080,were tested by MTT assay.Results and conclusion Thirteen compounds were synthesized,and the structures of twelve new compounds were confirmed by 1H-NMR and MS.Eight compounds showed potent antiproliferative activities,and compounds 4a and 5a displayed promising activities which was three and four times better than gefitinib,respectively.