新型噻唑并[3,2-a]嘧啶衍生物的合成及其抗肿瘤活性
收稿日期: 2014-08-31
修回日期: 2014-11-09
网络出版日期: 2014-11-18
基金资助
国家自然科学基金(No. 21462056)、遵义医学院博士科研启动基金(No. F-631)、贵州省科技厅(Nos. 黔科合LH字[2014]7565号, 黔科合LH字[2014]7557号, 黔科合人才团队[2014]4002号)和贵州省教育厅(No. 黔科合人才团队字[2012]03号)资助项目.
Synthesis and Antiproliferative Activity of Novel Thiazolo[3,2-a]pyrimidine Derivates
Received date: 2014-08-31
Revised date: 2014-11-09
Online published: 2014-11-18
Supported by
Project supported by the National Natural Science Fundation of China (No. 21462056), the Priming Scientific Research Foundation for Doctoral Program of Zunyi Medical College (No. F-631), the Department of Science and Technology of Guizhou Province (Nos. [2014]7565, [2014]7557, [2014]4002) and the Education Department of Guizhou Province (No. QJHRCTDZ-2012-03).
以取代苯肼盐酸盐为原料, 通过Vilsmeier-Haack, Biginelli和Knoevenagel等多步反应合成了9个含有吡唑取代基的噻唑并[3,2-a]嘧啶衍生物, 并利用IR, 1H NMR, 13C NMR, ESI-MS和HRMS对目标化合物进行了结构表征. 用四甲基偶氮唑盐(MTT)法测试了目标产物对人前列腺癌PC-3细胞和人肝癌HepG2细胞的体外抗增殖活性, 部分化合物表现出了较好的生物活性, 其中化合物5b, 5c, 5g和5i对PC-3细胞的抗肿瘤活性优于阳性对照药5-氟尿嘧啶, IC50值分别为29.98, 27.69, 26.36和12.56 μmol/L. 进一步的研究表明, 化合物5i能够诱导PC-3细胞凋亡, 并使其周期阻滞在G2/M期.
关键词： 噻唑并[3,2-a]嘧啶; 抗肿瘤活性; 细胞凋亡; 细胞周期
张磊 , 林娅 , 王京 , 朱心玲 , 姚秋丽 , 姚其正 . 新型噻唑并[3,2-a]嘧啶衍生物的合成及其抗肿瘤活性[J]. 有机化学, 2015 , 35(2) : 497 -504 . DOI: 10.6023/cjoc201408039
Nine novel thiazolo[3,2-a]pyrimidine derivatives with pyrazole substituent were synthesized from substituted phenylhydrazines via Vilsmeier-Haack, Biginelli and Knoevenagel reactions and characterized by IR, 1H NMR, 13C NMR, ESI-MS and HRMS. The antiproliferative activities of target compounds against human prostate cancer PC-3 and human hepatoma HepG2 cell lines were evaluated by methyl thiazolyl tetrazolium (MTT) assay. The results displayed that several compounds showed moderate to potent antitumor activity. Particularly, compounds 5b, 5c, 5g and 5i exhibited slightly stronger antitumor activity than positive control 5-fluorouracil (5-FU) against PC-3 cells with IC50 values of 29.98, 27.69, 26.36 and 12.56 μmol/L. Moreover, the cellular mechanisms showed that compound 5i could induce apoptosis and G2/M cell cycle arrest of PC-3 cells.
Key words： thiazolo[3,2-a]pyrimidine; anticancer activity; cell apoptosis; cell cycle
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