氟化及双功能化3-苯基色满-4-酮（异黄酮）芳香酶抑制剂的研究
Investigation of fluorinated and bifunctionalized 3-phenylchroman-4-one (isoflavanone) aromatase inhibitors.
作者信息
Amato Erica, Bankemper Tony, Kidney Rebecca, Do Thuy, Onate Alma, Thowfeik Fathima Shazna, Merino Edward J, Paula Stefan, Ma Lili
机构信息
Department of Chemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, United States.
Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, United States.
出版信息
Bioorg Med Chem. 2014 Jan 1;22(1):126-34. doi: 10.1016/j.bmc.2013.11.045. Epub 2013 Dec 5.
Abstract
Fluorinated isoflavanones and bifunctionalized isoflavanones were synthesized through a one-step gold(I)-catalyzed annulation reaction. These compounds were evaluated for their in vitro inhibitory activities against aromatase in a fluorescence-based enzymatic assay. Selected compounds were tested for their anti-proliferative effects on human breast cancer cell line MCF-7. Compounds 6-methoxy-3-(pyridin-3-yl)chroman-4-one (3c) and 6-fluoro-3-(pyridin-3-yl)chroman-4-one (3e) were identified as the most potent aromatase inhibitors with IC₅₀ values of 2.5 μM and 0.8 μM. Therefore, these compounds have great potential for the development of pharmaceutical agents against breast cancer.
摘要
通过一步金（I）催化的环化反应合成了氟化异黄酮和双官能化异黄酮。在基于荧光的酶促测定中评估了这些化合物对芳香酶的体外抑制活性。对选定的化合物进行了对人乳腺癌细胞系MCF-7的抗增殖作用测试。化合物6-甲氧基-3-（吡啶-3-基）色满-4-酮（3c）和6-氟-3-（吡啶-3-基）色满-4-酮（3e）被鉴定为最有效的芳香酶抑制剂，IC₅₀值分别为2.5 μM和0.8 μM。因此，这些化合物在开发抗乳腺癌药物方面具有巨大潜力。
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