有机化学 ›› 2024, Vol. 44 ›› Issue (11): 3497-3504.DOI: 10.6023/cjoc202403049 上一篇    下一篇

研究论文

新型对苯二甲酰胺衍生物的合成及抗肿瘤活性研究

顾一飞a,b, 吴彩菊a, 王思琪a, 张世琳a, 陆远a, 司鑫鑫a,*(), 蒋佰玲c,*()   

  1. a 江苏海洋大学药学院 江苏省海洋药物活性分子筛选重点实验室 江苏连云港 222005
    b 江苏省海洋资源开发研究院 江苏连云港 222005
    c 连云港市第二人民医院药学部 江苏连云港 222005
  • 收稿日期:2024-03-29 修回日期:2024-04-29 发布日期:2024-05-30
  • 基金资助:
    江苏海洋大学人才引进项目(KQ21044); 江苏省双创博士(JSSCBS20221615); 江苏海洋大学大学生实践创新计划(SY202211641640005)

Synthesis and Antitumor Activity of Novel Terephthalamide Derivatives

Yifei Gua,b, Caiju Wua, Siqi Wanga, Shilin Zhanga, Yuan Lua, Xinxin Sia,*(), Bailing Jiangc,*()   

  1. a Jiangsu Key Laborratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, Jiangsu 222005
    b Jiangsu Institute of Marine Resources Development, Lianyungang, Jiangsu 222005
    c Department of Pharmacy, The Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu 222005
  • Received:2024-03-29 Revised:2024-04-29 Published:2024-05-30
  • Contact: *E-mail:jiangbailing2018@163.com;sixinxinyd@163.com
  • Supported by:
    Research Project for Talent Introduction of Jiangsu Ocean University(KQ21044); Doctor of Jiangsu Double Innovation(JSSCBS20221615); College Student’s Practice Innovation Program of Jiangsu Ocean University(SY202211641640005)

为了寻找结构新颖、活性较好的抗肿瘤化合物, 采用拼合原理设计合成了一系列新型对苯二甲酰胺衍生物, 并测定了目标化合物对PANC-1(人胰腺癌细胞)、MDA-MB-231(人乳腺癌细胞)、SGC7901(人胃癌细胞)三株人类肿瘤细胞的抗增殖活性. 其中N1-(4-甲氧基苄基)-N4-(3-甲氧基苯基)-N1-(3,4,5-三甲氧基苯基)对苯二甲酰胺(TF)是抗PANC-1细胞增殖活性最佳的化合物, IC50为0.13 µmol/L, 优于阳性对照5-氟尿嘧啶(16.22 μmol/L). 表型实验显示化合物TF能够以剂量依赖的形式抑制PANC-1细胞集落形成, 并且可以减弱PANC-1细胞黏附、迁移和侵袭的作用. 这些结果表明, 化合物TF可作为一种潜在的抗肿瘤药物.

关键词: 对苯二甲酰胺, 抗肿瘤活性, 合成

In order to search for new structural antitumor drugs, a series of terephthalamide derivatives were designed and synthesized, and their antiproliferative activities against human tumor cell lines (PANC-1, MDA-MB-231 and SGC7901) were determined. N1-(4-Methoxybenzyl)-N4-(3-methoxyphenyl)-N1-(3,4,5-trimethoxyphenyl)terephthalamide (TF) was identified as the most potent compound in antiproliferation against PANC-1 cells with the value of 0.13 μmol/L, which was better than the positive control 5-fluorouracil (16.22 μmol/L). Further mechanistic studies showed that compound TF could inhibit the clonal proliferation in a dose-dependent manner. In addition, compound TF can reduce the adhesive, migrational and invasive of PANC-1cells. These results indicated that compound TF might be developed the antitumor drug.

Key words: terephthalamide, antivity, synthesis