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| 氮唑类衍生物的合成及抗乳腺癌细胞增殖活性 |
| 蔡艺1,2,杨帆1,2,柴晓云2,汪亭2,吴秋业1,2,孟庆国1* |
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(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
*通信作者) |
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| 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1HNMR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。 |
| 关键词: 乳腺肿瘤 氮唑类 酮康唑 合成 |
| DOI：10.16781/j.0258-879x.2016.03.0349 |
| 投稿时间：2015-07-25修订日期：2016-01-06 |
| 基金项目: |
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| Synthesis and anti-breast cancer activity of azole derivatives |
| CAI Yi1,2,YANG Fan1,2,CHAI Xiao-yun2,WANG Ting2,WU Qiu-ye1,2,MENG Qing-guo1* |
(1. Department of Pharmaceutical Chemistry, School of Pharmacy, Yantai University, Yantai 264005, Shandong, China;
2. Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| 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 1HNMR and 13CNMR. The synthesized azole derivatives have greater inhibitory effects than tamoxifene against breast cancer MDA-MB-231 cells. |
| Key words: breast neoplasm azoles ketoconazde synthesis |
