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首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: new lead compounds for the development of anticancer agents.
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Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: new lead compounds for the development of anticancer agents.

机译:非甾体类抗炎药及其类似物可作为醛基酮还原酶AKR1C3的抑制剂:用于开发抗癌药的新的先导化合物。

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摘要

Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin, flufenamic acid, and related compounds have been recently identified as potent inhibitors of AKR1C3. We report that some other NSAIDs (diclofenac and naproxen) also inhibit AKR1C3, with the IC(50) values in the low micromolar range. In order to obtain more information about the structure-activity relationship and to identify new leads, a series of compounds designed on the basis of NSAIDs were synthesized and screened on AKR1C3. The most active compounds were 2-[(2,2-diphenylacetyl)amino]benzoic acid 4 (IC(50)=11microM) and 3-phenoxybenzoic acid 10 (IC(50)=0.68microM). These compounds represent promising starting points for the development of new anticancer agents.
机译:非甾体类抗炎药(NSAIDs),如消炎痛,氟苯那酸和相关化合物,最近被确定为AKR1C3的有效抑制剂。我们报告说,其他一些NSAID(双氯芬酸和萘普生)也抑制AKR1C3,其IC(50)值处于低微摩尔范围。为了获得有关构效关系的更多信息并确定新的先导,合成了一系列基于NSAID设计的化合物,并在AKR1C3上进行了筛选。活性最高的化合物是2-[((2,2-二苯基乙酰基)氨基]苯甲酸4(IC(50)= 11microM)和3-苯氧基苯甲酸10(IC(50)= 0.68microM)。这些化合物代表了开发新的抗癌药的有希望的起点。

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