论文部分内容阅读
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 evaluate their anti-tumor activity. Methods The substituted acetophenones were used as starting materials. The corresponding substituted β-keto esters were obtained by the Claisen condensation of diethyl carbonate and then the substituted salicylaldehyde was condensed with Knoevenagel to give the target compounds. The antitumor activity of some of the target compounds was preliminarily evaluated using human acute promyelocytic leukemia cell line HL-60 and human breast cancer cell line T47D. Results Eighteen target compounds were synthesized, of which 13 were not reported in the literature. The structures of target compounds were confirmed by 1H NMR and FT-IR. The inhibitory activity of compound Ⅲ15 on human breast cancer cell T47D was stronger with IC50 value of 38μmol·L-1. The inhibitory activity of compound Ⅲ1, Ⅲ2 and Ⅲ15 on human acute promyelocytic leukemia HL-60 cells was better 37,36,16μmol·L-1. Conclusion 3-benzoyl-2H-1-benzopyran-2-one derivatives as new tumor suppressor, the structure-activity relationship deserves further study.