N-苯甲酰基邻氨基苯甲酸衍生物作为醛酮还原酶 AKR1C3 的选择性抑制剂。
N-Benzoyl anthranilic acid derivatives as selective inhibitors of aldo-keto reductase AKR1C3.
机构信息
Institute of Biochemistry, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
出版信息
Bioorg Med Chem Lett. 2012 Sep 15;22(18):5948-51. doi: 10.1016/j.bmcl.2012.07.062. Epub 2012 Jul 22.
Abstract
Human aldo-keto reductases AKR1C1-AKR1C3 are involved in the biosynthesis and inactivation of steroid hormones and prostaglandins and thus represent attractive targets for the development of new drugs. We synthesized a series of N-benzoyl anthranilic acid derivatives and tested their inhibitory activity on AKR1C enzymes. Our data show that these derivatives inhibit AKR1C1-AKR1C3 isoforms with low micromolar potency. In addition, five selective inhibitors of AKR1C3 were identified. The most promising inhibitors were compounds 10 and 13, with IC(50) values of 0.31 μM and 0.35 μM for AKR1C3, respectively.
摘要
人醛酮还原酶 AKR1C1-AKR1C3 参与甾体激素和前列腺素的生物合成和失活，因此代表了开发新药的有吸引力的靶标。我们合成了一系列 N-苯甲酰邻氨基苯甲酸衍生物，并测试了它们对 AKR1C 酶的抑制活性。我们的数据表明，这些衍生物以低微摩尔的效力抑制 AKR1C1-AKR1C3 同工酶。此外，还鉴定了五种 AKR1C3 的选择性抑制剂。最有前途的抑制剂是化合物 10 和 13，它们对 AKR1C3 的 IC50 值分别为 0.31 μM 和 0.35 μM。
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