氮唑类衍生物的合成及抗乳腺癌细胞增殖活性

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1HNMR和13CNMR确证结构.大多数目标化合物对乳腺癌细胞MDA-MB231的抑制活性优于阳性对照药他莫昔芬.

Synthesis and anti-breast cancer activity of azole derivatives

Objective Selecting antifungal drug ketoconazole as lead compound, we designed and synthesized a new series of efficient, low toxicity azole derivatives to explore its anti-breast cancer activity. Methods Based on the docking mode of ketoconazole with estrogen receptor, eleven derivatives, which 2, 4-dichlorophenyl and triazole ring were retained and the side chains were modified, were designed and synthesized. Then the in vitro anticancer activities on 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 were reported firstly and confirmed by 1H NMR and 13C NMR. Biological studies showed that the synthesized azole derivatives had better inhibitory effects than tamoxifene on breast cancer cells MDB-MA-231.