含噻吩并[3,2-d]嘧啶的查尔酮类化合物的合成和抗增殖活性

Design, synthesis and antiproliferative activity of chalcone derivatives bearing thieno[3,2-d]pyrimidine moiety

摘要:

运用药物分子片段原理及拼合原理，设计并合成了10个含噻吩并[3,2-d]嘧啶的查尔酮类衍生物，并对该类化合物的体外抗对肿瘤细胞增殖活性进行初步研究。目标化合物的结构通过1H NMR、13C NMR和HRMS (ESI)表征。以人肺腺癌细胞株A549、人肝癌细胞株HepG2和人前列腺癌细胞株PC-3三种肿瘤细胞为测试细胞株，采用MTT法评价了目标化合物的抗增殖活性。体外活性实验表明，10个化合物对三种肿瘤细胞株均具有很好的抑制活性。其中化合物Ⅶh活性突出，对三种肿瘤细胞株的IC50 值分别为0.87 μmol/L、2.43 μmol/L和2.02 μmol/L，优于阳性对照药索拉非尼。含噻吩并[3,2-d]嘧啶的查尔酮类化合物具有很好的抗肿瘤活性，值得进一步研究。

Abstract:

Ten novel chalcone derivatives bearing thieno[3,2-d]pyrimidine moiety were successfully designed and synthesized based on the principle of drug molecular fragment and splicing principle and evaluate their antiproliferative activities. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and MS. A549, HepG2 and PC-3 cell lines were employed to evaluate anticancer activities of the target compounds using MTT assay in vitro．All the target compounds showed excellent antiproliferative activities against all tested cancer cell lines. Among them, compound Ⅶh exhibited remarkable inhibitory activity against A549, HepG2 and PC-3 cell lines with IC50 value of 0.87 μmol/L, 2.43 μmol/L and 2.02 μmol/L, respectively, which were more potent than that of the positive control sorafenib. Chalcone derivatives bearing thieno[3,2-d]pyrimidine moiety showed excellent antiproliferative activities, and could serve as a scaffold for anticancer drug development.