3-苯甲酰基-2H-1-苯并吡喃-2-酮衍生物的设计、合成及抗肿瘤活性

Synthesis and antitumor activities of 3-benzoyl-2H-1-benzopyran-2-one derivatives

目的设计合成3-苯甲酰基-2H-1-苯并吡喃-2-酮衍生物,并评价其抗肿瘤活性。方法以取代苯乙酮为原料,首先与碳酸二乙酯经Claisen缩合得到相应的取代β-酮酸酯,再与取代水杨醛经Knoevenagel缩合,同时环合得到目标化合物。采用人急性早幼粒白血病细胞HL-60及人乳腺癌细胞T47D对部分目标化合物的抗肿瘤活性进行初步评价。结果合成了18个目标化合物,其中13个未见文献报道,目标化合物的结构经核磁共振氢谱和红外光谱确证。化合物Ⅲ15对人乳腺癌细胞T47D的抑制活性较强,IC50值为38μmol·L-1;化合物Ⅲ1、Ⅲ2、Ⅲ15对人急性早幼粒白血病细胞HL-60的抑制活性较好,IC50值分别为37、36、16μmol·L-1。结论3-苯甲酰基-2H-1-苯并吡喃-2-酮衍生物作为新型肿瘤抑制剂,其构效关系值得进一步研究。

Aim To design and synthesize 3-benzoyl-2H-1-benzopyran-2-one derivatives,and to assay their antitumor activities.Methods Substituted acetophenones were reacted with diethyl carbonate via Claisen condensation to obtain the corresponding β-keto esters,which were further treated with substituted salicylaldehydes through the Knoevenagel condensation and cyclization at the same time to yield the target compounds.The antitumor activities of some target compounds obtained were evaluated on the human acute promyelocy-tic leukemia cells HL-60 and the human breast cancer cells T47D in vitro.Results Eighteen compounds were obtained and thirteen of them were not reported in the literature,and their structures were characterized by 1H-NMR and IR.Among the compounds tested,compound Ⅲ15 showed good activity against T47D cells,with IC50 of 38 μmol·L-1;compounds Ⅲ1,Ⅲ2 and Ⅲ15 exhibited good activities against HL-60 cells,with IC50s of 37 μmol·L-1,36 μmol·L-1 and 16 μmol·L-1 respectively.Conclusion The structure-activity relationships of 3-benzoyl-2H-1-benzopyran-2-one derivatives,as a novel type of tumor inhibitor,should be investigated furtherly.