4,5-二氢-1H-硫色烯[4,3-d]嘧啶类化合物合成及抗肿瘤细胞增殖活性研究

以苯硫酚为起始原料经Michael加成,环合得到硫色满酮,再利用3组分(醛、酮、氨基脒)反应合成了4,5-二氢-1H-硫色烯[4,3-d]嘧啶类目标化合物,所合成的5个目标化合物未见文献报道,其结构经核磁共振氢谱和质谱确证。采用MTT法,以吉非替尼(gefitinib)为阳性对照药,测定了目标化合物对肺腺癌A549细胞和非小细胞肺癌H460细胞的体外抗肿瘤增殖活性。化合物GDX1和GDX2对A549和H460的抑制活性较强,其IC50值分别为0.77、0.67、4.38、3.78μmol/L。实验表明4,5-二氢-1H-硫色烯[4,3-d]嘧啶类化合物是一类具有新型骨架结构的抗肿瘤化合物,值得进一步研究。

Synthesis and Antiproliferative Activity of Novel 4,5-Dihydro-1H-thiochromeno[4,3-d]pyrimidine Derivatives

Five of novel 4,5-dihydro-1H-thiochrochromeno pyrimidine derivatives were synthesized from single step reaction under aldehyde,ketone and aminoamidines,in which the ketones belonged to thiochromanone derivatives prepared by Michael addition and cyclization from thiophenols as the start materials.The target compounds are characterized by NMR and MS.The antiproliferative activities of the target compounds have been evaluated in vitro against two human cancer cell lines including A549（human alveolar adenocarcinoma cell） and H460（human lung cancer） by MTT assay with gefitinib,a standard anticancer drug,as the positive control.The target compounds GDX1 and GDX2 showed good activity in vitro against A549 and H460 cells in vitro,with the half maximal inhibitory concentration of 0.77,0.67 and 4.38,3.78 μmol/L,respectively.The screening result indicates the 4,5-dihydro-1H-thiochrochromeno pyrimidine scaffold becomes a novel moiety with antiproliferative activity and further efforts aiming at developing potent antitumor agents with 4,5-dihydro-1H-thiochrochromeno pyrimidine scaffold would be continued in the future.