新结构嘧啶类化合物合成及抗肿瘤活性筛选.pdfVIP

2011;31(5) 南方医科大学学报（J South Med Univ ） ·875 · ·基础研究· 新结构嘧啶类化合物的合成及抗肿瘤活性筛选 游文玮，赵培亮，邹 敏，周中振，段安娜，吴曙光 南方医科大学药学院，广东 广州 510515 摘要：目的合成具有抗肿瘤活性的新型CDKs 抑制剂，并评价其抗肿瘤活性。方法根据生物活性叠加原理，将1-（甲磺酰 4 2 基）哌啶-4-氨和嘧啶杂环片段合理组合，设计合成了5个结构新颖的N -取代苯胺基-N -(1-甲磺酰基哌啶-4-氨基)-5-硝基 嘧啶类化合物3a~3e。结果 目标化合物的结构经质谱和核磁共振氢谱等表征确认。采用MTT 法测试了目标化合物抑制 肿瘤细胞增殖活性。测试结果表明，部分化合物对MCF-7 (人乳腺癌细胞)肿瘤细胞有弱的细胞毒性，而对HepG2 (人肝 癌细胞)没有抑制活性，表现出一定的选择性。结论化合物3b 对MCF-7 (人乳腺癌细胞)肿瘤细胞有较强的抑制活性 -1 (IC = 13.6 μmol ·L )。初步的构效关系研究表明化合物的立体结构可能对其抗肿瘤活性影响较大。 50 关键词：嘧啶；合成；抗肿瘤活性 中图分类号：R914.5 文献标志码：A 文章编号：1673-4254（2011）05-0875-03 Synthesis and antitumor activities of pyrimidines YOU Wen-wei, ZHAO Pei-liang, ZOU Min, ZHOU Zhong-zhen, DUAN An-na, WU Shu-guang College of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China Abstract: Objective To synthesize cyclin-dependent kinase (CDKs) inhibitors and assay their antitumor activities. Methods A series of pyrimidines containing different arylamino and 1-(methylsulfonyl)piperidin moieties were designed by combining the segments 1-(methylsulfonyl)piperidin and pyrimidine heterocycles according to the super-postion principle of the reinforcement of biological activities. Results Their structures were characterized by MS and 1H NMR spectra and all the synthesized compounds were screened for their antimicrobial activity with MTT assay. Conclusion The preliminary bioassay showed that compound 3b displayed good antitumor activity (IC50=13.6 μmol/L). The preliminary structure activity relationship