氮唑类衍生物的合成及抗乳腺癌细胞增殖活性  

Synthesis and anti-breast cancer activity of azole derivatives

作　　者：蔡艺[1,2] 杨帆[1,2] 柴晓云[2] 汪亭[2] 吴秋业[1,2] 孟庆国[1] 

机构地区：[1]烟台大学药学院药物化学教研室,烟台264005 [2]第二军医大学药学院有机化学教研室,上海200433

出　　处：《第二军医大学学报》2016年第3期349-354,共6页Academic Journal of Second Military Medical University

摘　　要：目的以抗真菌药酮康唑为先导化合物,设计合成一类新型、高效、低毒的氮唑类衍生物,探究其抗乳腺癌细胞增殖活性。方法根据前期酮康唑与雌激素受体的计算机模拟对接结果,保留先导化合物酮康唑分子母核结构中的2,4-二氯苯基和三氮唑环,对侧链进行改造,合成了11个氮唑类衍生物。以他莫昔芬为阳性对照药,以乳腺癌细胞MDA-MB-231和MCF-7为测试瘤株,用MTT法测定目标化合物的体外抗乳腺癌细胞增殖活性。结果和结论合成的目标化合物均为首次报道,并经1 HNMR和13CNMR确证结构。大多数目标化合物对乳腺癌细胞MDA-MB-231的抑制活性优于阳性对照药他莫昔芬。Objective To design and synthesize a new series of efficient, low toxicity azole derivatives using antifungal drug ketoconazole as the lead compound and to explore their anti-breast cancer activity. Methods Based on the docking mode of ketoconazole with estrogen receptor, We designed and synthesized eleven derivatives, whose 2, 4-dichlorophenyl and triazole ring were retained and the side chains were modified. Then the in vitro anticancer activities against breast cancer cells MDA- MB-231 and MCF-7 were determined by MTT using tamoxifene as the positive control drug. Results and Conclusion The synthesized compounds have been reported for the first time and they have been confirmed by 1 HNMR and n CNMR. The synthesized azole derivatives have greater inhibitory effects than tamoxifene against breast cancer MDA-MB-231 cells.

关 键 词：乳腺肿瘤 氮唑类 酮康唑 合成 

分 类 号：R916.42[医药卫生—药学] R737.9