新型噻唑并[3,2-a]嘧啶衍生物的合成及其抗肿瘤活性

Synthesis and Antiproliferative Activity of Novel Thiazolo[3,2-a]pyrimidine Derivates

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Hep G2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12.56μmol/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.

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, 13 C NMR, ESI-MS and HRMS. The antiproliferative activities of target compounds against human prostate cancer PC-3 and human hepatoma Hep G2 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.