有机化学 ›› 2019, Vol. 39 ›› Issue (3): 821-829.DOI: 10.6023/cjoc201807022 上一篇    下一篇

研究论文

新型异长叶烷基二氢嘧啶硫酮类衍生物的合成及其抗肿瘤活性研究

马崇慧a, 吴陈亮a, 王芸芸a, 黄真真b, 张强健a, 董阜豪a, 谷文a,c, 单宇b, 王石发a,c   

  1. a 南京林业大学化学工程学院 南京 210037;
    b 江苏省中国科学院植物研究所 南京 210014;
    c 南京林业大学林业资源高效加工利用协同创新中心 南京 210037
  • 收稿日期:2018-07-11 修回日期:2018-09-24 出版日期:2019-03-25 发布日期:2018-10-20
  • 通讯作者: 单宇, 王石发 E-mail:attilayu@hotmail.com;wangshifa65@163.com
  • 基金资助:

    国家自然科学基金(No.31470592)资助项目.

Synthesis and Antitumor Activity of Novel Isolongifolic-Alkyl Dihydropyrimidinethione Derivatives

Ma Chonghuia, Wu Chenlianga, Wang Yunyuna, Huang Zhenzhenb, Zhang Qiangjiana, Dong Fuhaoa, Gu Wena,c, Shan Yb, Wang Shifaa,c   

  1. a College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037;
    b Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014;
    c Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing 210037
  • Received:2018-07-11 Revised:2018-09-24 Online:2019-03-25 Published:2018-10-20
  • Contact: 10.6023/cjoc201807022 E-mail:attilayu@hotmail.com;wangshifa65@163.com
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 31470592).

以异长叶烷酮为起始物,经羟醛缩合、环化等手段,合成了12种异长叶烷基二氢嘧啶硫酮类衍生物,通过1H NMR、13C NMR及高分辨质谱(HRMS)对其结构进行了表征,通过X射线衍射分析测定了化合物3e的晶体结构.探索了这些衍生物对人乳腺癌细胞(MDA-MB-231)、人宫颈癌细胞(HeLa)、人肝癌细胞(HepG-2)等三种癌细胞和一种正常细胞即小鼠巨噬细胞(RAW-264.7)的体外抗增殖活性.结果表明,这12种化合物显示出较好的抗肿瘤活性,其IC50值在3.12~44.28 μmol/L范围内.其中,化合物3j对MDA-MB-231细胞表现出最强的抗肿瘤活性(IC50=3.12 μmol/L),化合物3g对HeLa细胞表现出最强的抗肿瘤活性(IC50=4.04 μmol/L),化合物3k对HepG-2细胞表现出最强的抗肿瘤活性(IC50=5.43 μmol/L).此外,化合物3j将MDA-MB-231细胞阻滞在G0/G1期,并以剂量依赖的方式诱导MDA-MB-231细胞的早期凋亡.

关键词: 异长叶烷酮, 二氢嘧啶硫酮类衍生物, 抗肿瘤活性

In this work, twelve dihydropyrimidinethione derivatives have been synthesized from isolongifolanone by aldol and cyclization reactions. The chemical structures were characterized by 1H NMR, 13C NMR and high resolution mass spectrometry (HRMS), and the structure of compound 3e was determined by X-ray single crystal diffraction. Their in vitro cytotoxicity against three cancer cell lines breast (MDA-MB-231), cervix (HeLa), liver (HepG-2) and one normal cell line mouse macrophages (Raw-264.7) were investigated. It was shown that these 12 compounds had good antitumor activity with IC50 values of 3.12~44.28 μmol/L. Among them, compounds 3j, 3g, and 3k had the best antitumor activity against MDA-MB-231 cells (IC50=3.12 μmol/L), HeLa cells (IC50=4.04 μmol/L) and HepG-2 cells (IC50=5.43 μmol/L), respectively. In addition, compound 3j arrested the cells in the G0/G1 phase of the MDA-MB-231 cell cycle and induced the early apoptosis of MDA-MB-231 cells in a dose-dependent manner.

Key words: isolongifolanone, dihydropyrimidinethione derivatives, antitumor activity