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

作　　者：曹阳 李前 崔文慧 王亚玲 司鑫鑫 CAO Yang;LI Qian;CUI Wen-hui;WANG Ya-ling;SI Xin-xin(School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210093,China;Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,Jiangsu Ocean University,Lianyungang 222005,China;Jiangsu Deyuan Pharmaceutical Co.,Ltd.,Lianyungang 222047,China)

机构地区：[1]南京大学化学化工学院,江苏南京210093 [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 [3]江苏德源药业股份有限公司,江苏连云港222047

出　　处：《精细化工中间体》2024年第3期31-37,共7页Fine Chemical Intermediates

基　　金：中国博士后科学基金(2023M741444)。

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=3.61μmol/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、10μmol/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、10μmol/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、10μmol/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。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(IC_(50)=3.61μmol/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 10μmol/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 10μmol/L for 48 h,the migration rates declined 25%, 46%, and 49% vs the control group, respectively. After being treated with II-1 at concentrationof 1, 5, and 10 μmol/L for 48 h, the relative invasion abilities of PANC-1 cells declined 64%, 79%, and 89% vs thecontrol group, respectively. These experimental results indicate that II-1 has high inhibitory effects on PANC-1cells, 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 

分 类 号：R914.5[医药卫生—药物化学] O621.3[医药卫生—药学] TQ463.53[理学—有机化学]