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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 class of high efficiency and low toxicity azole derivatives with antifungal ketoconazole as the lead compound and explore its antiproliferative activity against breast cancer cells. Methods Based on the computer simulation of the conjugation of ketoconazole and estrogen receptor, the side chain of 2,4-dichlorophenyl and triazole ring in the precursor of ketoconazole remained unchanged and the side chain was modified to synthesize Eleven azole derivatives were obtained. Taking tamoxifen as the positive control drug, the breast cancer cells MDA-MB-231 and MCF-7 were used as the test tumor strains, and the anti-proliferation activities of the target compounds against breast cancer cells were measured by MTT assay. RESULTS AND CONCLUSIONS The target compounds were first reported and confirmed by 1 H NMR and 13CNMR. The inhibitory activity of most of the target compounds on breast cancer cells MDA-MB-231 was superior to that of the positive control drug tamoxifen.