吲哚-1,3,4-(噁)二唑类衍生物的合成及其体外抗肿瘤活性研究
Synthesis and antitumor activity in vitro of indole-1,3,4-oxadiazole derivatives
郑煦阳 1李凌宇 2胡玥 2尚海 2邹忠梅1
作者信息
- 1. 天津中医药大学 研究生院,天津 301600;中国医学科学院 北京协和医学院 药用植物研究所,北京 100193
- 2. 中国医学科学院 北京协和医学院 药用植物研究所,北京 100193
- 折叠
摘要
目的 合成吲哚-1,3,4-(噁)二唑类衍生物,并进行体外抗肿瘤活性研究.方法 以吲哚-3-甲酰肼为起始原料,通过[4+1]环加成反应、水解反应、缩合反应得到目标化合物.采用MTT法测试目标化合物对HeLa、SCG-7901 和MDA-MB-231 细胞的体外抗肿瘤活性.采用克隆形成实验考察化合物 6f对SCG-7901 细胞增殖的影响.采用Annexin V-APC/PI双染法检测化合物 6f对SCG-7901 细胞凋亡和坏死的影响.采用DAPI染色法检测化合物 6f对SCG-7901 细胞凋亡核染色质形态学的影响.采用DCFH-DA染色法检测化合物 6f对SCG-7901 细胞中活性氧含量的影响.结果 合成了 15 个吲哚-1,3,4-(噁)二唑类衍生物,其结构经 1H-NMR、13C-NMR和HR-ESI-MS确证.部分化合物表现出良好的抗肿瘤活性,其中化合物 6f对HeLa、SCG-7901 和MDA-MB-231 3 种肿瘤细胞株均表现出明显的抗增殖作用,且具有一定的选择性.进一步研究表明,化合物 6f以浓度相关的方式促进细胞产生活性氧,抑制细胞增殖,诱导细胞凋亡.结论 部分吲哚-1,3,4-(噁)二唑类衍生物表现出良好的抗肿瘤活性,为该类化合物的进一步抗肿瘤活性研究提供思路.
Abstract
Objective To synthesize indole-1,3,4-oxadiazole derivatives and investigate antitumor activities in vitro.Methods Taking 1H-indole-3-carbohydrazide as the starting material,the target compounds were obtained through[4+1]cycloaddition reaction,hydrolysis reaction and condensation reaction.Antitumor activity in vitro of target compounds against HeLa,SCG-7901,and MDA-MB-231 cells were evaluated by MTT assay.The effect of compound 6f against the growth of SCG-7901 cells was assessed by colony formation assay,the effect of it on apoptosis and necrosis in SCG-7901 cells was detected using Annexin V-APC/PI double staining method,the effect of it on nuclear chromatin morphological changes of SCG-7901 cells were examined using DAPI staining method,and the effect of it on contents of reactive oxygen species(ROS)in SCG-7901 cells was detected using DCFH-DA staining method.Results Fifteen indole-1,3,4-oxadiazole derivatives were synthesized and their structures were characterized by 1H-NMR,13C-NMR,and HR-ESI-MS.Some compounds exhibited significant antitumor activity,among which compound 6f exhibited significant anti-proliferative effects against all three tumor cell lines and had certain selectivity.Further research has shown that compound 6f promoted cell production of ROS generation,inhibited cell proliferation,and induced cell apoptosis in a concentration dependent manner.Conclusion Some indole-1,3,4-oxadiazole derivatives have shown good antitumor activity,providing ideas for further research on the anti-tumor activity of these compounds.
关键词
吲哚-1,3,4-(噁)二唑/合成/抗肿瘤/SCG-7901细胞/活性氧Key words
indole-1,3,4-oxadiazole/synthesis/antitumor/SCG-7901 cell/ROS引用本文复制引用
基金项目
国家重大新药创制科技重大专项(2019ZX09735002)
中国医学科学院医学与健康科技创新工程项目(2022-I2M-1-017)
出版年
2024
NETL
NSTL
万方数据