吲哚并四氢呋喃-咪唑盐杂合物的合成及细胞毒活性研究

发布时间：2019-04-28 07:15

【摘要】：从色醇出发,通过Sharpless环氧化、酰胺化、偶联和成盐四步反应合成了一系列新型的吲哚并四氢呋喃-咪唑盐杂合物,其结构经~1H NMR,~(13)CNMR,HRMS以及X射线单晶衍射确定.对合成的新化合物进行了体外抗肿瘤细胞毒活性筛选,结果表明,1-((3aR,8aS)-3,3a-二氢-3a-羟基-2H-呋喃并[2,3-b]吲哚-8(8aH)-基)乙酮-3-(2-(萘-2-基)-2-氧乙基)-5,6-二甲基-1H-苯并[d]咪唑-3-溴盐(20)和1-((3aR,8aS)-3,3a-二氢-3a-羟基-2H-呋喃并[2,3-b]吲哚-8(8aH)-基)乙酮-3-(2-萘甲基))-5,6-二甲基-1H-苯并[d]咪唑-3-溴盐(22)具有较好的体外肿瘤生长抑制活性,对SMMC-7721、MCF-7和SW-480肿瘤细胞株的活性均优于顺铂(DDP),1-((3aR,8aS)-3,3a-二氢-3a-羟基-2H-呋喃并[2,3-b]吲哚-8(8a H)-基)乙酮-3-(2-溴苄基))-5,6-二甲基-1H-苯并[d]咪唑-3-溴盐(24)对SW-480肿瘤细胞株表现出较好的选择性细胞毒活性,其IC_(50)值约为顺铂的2.0倍.
[Abstract]:A series of novel indole tetrahydrofuran imidazolium salt complexes were synthesized by four steps of Sharpless epoxidation, amidation, coupling and salting. Their structures were determined by 1H NMR,~ (13) CNMR,HRMS and X ray single crystal diffraction. The new compounds were screened for their antitumor activity in vitro. The results showed that 1-(3aR, 3aR, 3aR, 3aR, 3aR, 3AR, 8aS)-3, 3a-dihydro-3a-hydroxy-2H-furan [2,3mb] indole-8 (8aH)-ethyl ketone-3-(2-(naphthalene-2-yl)-2-oxyethyl)-5,6-dimethyl-1H-benzo [d] Zol-3-bromate (20) and 1-(3aR, 8aS)-3, 3a-dihydro-3a-hydroxy-2H-furan [2,3mb] indole-8 (8aH)-ethyl ketone-3-(2-naphthalene methyl)-5,6-dimethyl-1H-benzo [d] imidazole-3-bromate (22) It has good tumor growth inhibition activity in vitro. The activity against SMMC-7721,MCF-7 and SW-480 tumor cell lines was better than that of cisplatin (DDP), 1-(3aR, P < 0.05, P < 0.01). 8aS)-3, 3a-dihydro-3a-hydroxy-2H-furan [2,3mb] indole-8 (8a H)-ethyl ketone-3-(2-bromobenzyl)-5,6-dimethyl-1H-benzo [d] imidazole-3-bromo salt (24 To SW-480 tumor cell line, it showed a good selective cytotoxic activity. Its IC_ (50) value is about 2.0 times higher than that of cisplatin.
【作者单位】：云南大学教育部自然资源药物化学重点实验室;中国科学院昆明植物研究所植物化学与西部植物资源持续利用国家重点实验室;
【基金】：国家自然科学基金(Nos.21662043,21462049,U1402227,21332007) 长江学者和创新团队发展计划(No.IRT13095) 云南省自然科学基金(No.2013FA028)资助项目~~
【分类号】：O626

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