新型1H-吡咯[2,3-c]并吡啶衍生物的合成和抗胰腺癌活性评价
Synthesis and Evaluation of Anti-pancreatic Cancer Activity of Novel 1H-Pyrrolo[2,3-c]pyridine Derivatives
曹阳 1李前 2崔文慧 2王亚玲 2司鑫鑫2
作者信息
- 1. 南京大学化学化工学院,江苏南京 210093;江苏德源药业股份有限公司,江苏连云港 222047
- 2. 江苏海洋大学江苏省海洋药物活性分子筛选重点实验室,江苏连云港 222005
- 折叠
摘要
胰腺癌恶性程度高、治疗药物少,开发具有抗胰腺癌活性的化合物有重要研究意义.通过改造1H-吡咯[2,3-c]并吡啶的氮1位,合成了 22个化合物,对所有化合物的抗胰腺癌活性进行了评价,Ⅱ-1活性表现较为突出(半抑制浓度IC50=3.61 μmol/L).利用细胞划痕实验及侵袭实验对Ⅱ-1的抗迁移能力及侵袭能力进行了研究.经1、5、10 μmol/L的Ⅱ-1处理24 h时,与对照组相比胰腺癌细胞(PANC-1细胞)迁移率分别下降28％、41％、54％;经1、5、10 μmol/L的Ⅱ-1处理48 h时,与对照组相比PANC-1迁移率分别下降25％、46％、49％;经1、5、10 μmol/L的Ⅱ-1处理48 h时,与对照组相比PANC-1细胞相对侵袭能力分别下降64％、79％、89％.实验结果表明:Ⅱ-1对PANC-1细胞具有较高的抑制活性,Ⅱ-1抑制PANC-1细胞迁移及侵袭能力也较为突出.
Abstract
Pancreatic cancer has a high malignancy rate and there are very few therapeutic drugs.It is of great significance to develop compounds with anti-pancreatic cancer activity.By modifying the nitrogen at 1 position of 1H-pyrrolo[2,3-c]pyridine,22 compounds were synthesized.Compounds anti PANC-1 cell's activities were evaluated,Ⅱ-1 exhibited great activity(IC50=3.61 μmol/L).Anti migration and invasion abilities of Ⅱ-1 were studied using wound healing and invasion assay.After being treated with Ⅱ-1 at a concentration rate of 1,5,and 10 µmol/L for 24 h,the migration rates of PANC-1 cells declined 28% ,41% ,and 54% vs the control group,respectively.After being treated with Ⅱ-1 at a concentration rate of 1,5,and 10 μmol/L for 48 h,the migration rates declined 25% ,46% ,and 49% vs the control group,respectively.After being treated with Ⅱ-1 at concentration of 1,5,and 10 µmol/L for 48 h,the relative invasion abilities of PANC-1 cells declined 64% ,79% ,and 89% vs the control group,respectively.These experimental results indicate that Ⅱ-1 has high inhibitory effects on PANC-1 cells,and has prominent ability to inhibit the migration and invasion of PANC-1 cells.
关键词
化学合成/1H-吡咯[2,3-c]并吡啶/抗胰腺癌活性Key words
chemical synthesis/1H-pyrrolo[2,3-c]pyridine/anti pancreatic cancer activity引用本文复制引用
基金项目
中国博士后科学基金(2023M741444)
出版年
2024
NETL
NSTL
万方数据