COX-2 抑制剂尼美舒利类似物的先导优化以克服乳腺癌细胞中芳香酶抑制剂的耐药性。
Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase inhibitor resistance in breast cancer cells.
机构信息
Division of Tumor Cell Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
出版信息
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6733-5. doi: 10.1016/j.bmcl.2009.09.109. Epub 2009 Oct 3.
Abstract
A series of COX-2 selective inhibitor nimesulide derivatives were synthesized. Their anti-cell proliferation activities were evaluated with a long-term estrogen deprived MCF-7aro (LTEDaro) breast cancer cell line, which is the biological model of aromatase inhibitor resistance for hormone-dependent breast cancer. Compared to nimesulide which inhibited LTEDaro cell proliferation with an IC(50) at 170.30 microM, several new compounds showed IC(50) close to 1.0 microM.
摘要
合成了一系列 COX-2 选择性抑制剂尼美舒利衍生物。用长期去雌激素 MCF-7aro（LTEDaro）乳腺癌细胞系评估它们的抗细胞增殖活性，该细胞系是激素依赖性乳腺癌芳香酶抑制剂耐药的生物学模型。与尼美舒利的 IC（50）为 170.30μM 抑制 LTEDaro 细胞增殖相比，几种新化合物的 IC（50）接近 1.0μM。
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