苯并吡喃酮衍生物的体外抗增殖活性与标准化疗药物的比较。
In-vitro antiproliferative activity of benzopyranone derivatives in comparison with standard chemotherapeutic drugs.
机构信息
Florida A&M University, College of Arts and Sciences, Department of Chemistry, Tallahassee, FL, USA.
出版信息
Arch Pharm (Weinheim). 2011 Feb;344(2):102-10. doi: 10.1002/ardp.201000207. Epub 2010 Nov 29.
Abstract
The cytotoxic activities of five new benzopyranone derivatives containing basic amino side chain are described. Their cytotoxicities against ER(+) MCF-7 and ER(-) MDA-MB-231 human breast cancer cell lines, and Ishikawa human endometrial cell line were determined after 72 h drug exposure employing CellTiter-Glo assay at concentrations ranging from 0.01-1.0 × 10(5) nM. The antiproliferative activities of these compounds were compared to tamoxifen (TAM), 4-hydroxytamoxifen (4-OHT, active metabolite of tamoxifen), and raloxifene (RAL). In-vitro results indicated that compounds 9, 10, 12, and 13 were more potent than TAM against the human breast cancer cell lines with IC(50) < 20 µM. The in-silico structure-activity relationships of these compounds and their binding mode within the estrogen receptor (ER) binding site using AutoDock vina are discussed.
摘要
本文描述了五种含有碱性氨基酸侧链的苯并吡喃酮衍生物的细胞毒性活性。采用 CellTiter-Glo assay 在浓度范围为 0.01-1.0×10(5) nM 下，对这些化合物在 72 h 药物暴露后对 ER(+) MCF-7 和 ER(-) MDA-MB-231 人乳腺癌细胞系和 Ishikawa 人子宫内膜细胞系的细胞毒性进行了测定。将这些化合物的抗增殖活性与他莫昔芬（TAM）、4-羟基他莫昔芬（4-OHT，他莫昔芬的活性代谢物）和雷洛昔芬（RAL）进行了比较。体外结果表明，化合物 9、10、12 和 13 对人乳腺癌细胞系的活性均强于 TAM，IC(50) < 20 µM。本文还讨论了这些化合物的体外结构-活性关系及其与雌激素受体（ER）结合位点的结合模式，采用 AutoDock vina 进行模拟。
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