Sonego Juan M, Rivero Ezequiel M, Gargiulo Lucía, Lüthy Isabel, Alvarez Lautaro D, Veleiro Adriana S, Burton Gerardo
Departamento de Química Orgánica and UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Ciudad de Buenos Aires, Argentina.
Instituto de Biología y Medicina Experimental - CONICET, Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina.
Eur J Med Chem. 2014 Jul 23;82:233-41. doi: 10.1016/j.ejmech.2014.05.067. Epub 2014 May 28.
The antiestrogenic activity of three natural salpichrolides A, G and B (1, 3 and 4) and of five synthetic analogs containing an aromatic D ring and a simplified side chain (5-9), was evaluated on MCF-7 cells. The 2,3-ene-1-keto steroids 8 and 9 were obtained from 3β-acetoxy-17(13→18)-abeo-5αH-pregna-13,15,17-trien-20-one, the key step for these syntheses being a Wharton carbonyl rearrangement of a 1,2-epoxy-3-keto steroid to the allylic alcohol using hydrazine hydrate. The antiestrogenic activity was evaluated by performing dose-response experiments in ER(+) MCF-7 breast cancer cells. Dose-dependent proliferation was quantified via [(3)H]-thymidine incorporation after 3 days treatment. Salpichrolides A, G and B and analogs 5, 8 and 9 were active as antiestrogens with compound 9 being the most active of the synthetic analogs. Compounds 5 and 9 were also evaluated against the ER(-) cell line MDA-MB-231 and shown to be inactive.
评估了三种天然的萨尔皮氯内酯A、G和B（1、3和4）以及五种含有芳香D环和简化侧链的合成类似物（5 - 9）对MCF - 7细胞的抗雌激素活性。2,3 - 烯 - 1 - 酮甾体8和9是由3β - 乙酰氧基 - 17(13→18)-去甲 - 5αH - 孕甾 - 13,15,17 - 三烯 - 20 - 酮制得，这些合成的关键步骤是使用水合肼将1,2 - 环氧 - 3 - 酮甾体进行沃顿羰基重排为烯丙醇。通过在雌激素受体阳性（ER(+)）的MCF - 7乳腺癌细胞中进行剂量反应实验来评估抗雌激素活性。在3天处理后，通过[³H] - 胸腺嘧啶核苷掺入来定量剂量依赖性增殖。萨尔皮氯内酯A、G和B以及类似物5、8和9作为抗雌激素具有活性，其中化合物9是合成类似物中活性最强的。化合物5和9也针对雌激素受体阴性（ER(-)）细胞系MDA - MB - 231进行了评估，结果显示无活性。
