Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: New lead compounds for the development of anticancer agents
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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DOI：
10.1016/j.bmcl.2005.08.063
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发表时间：
2005-12-01
影响因子：
2.7
通讯作者：
Rizner, TL
中科院分区：
文献类型：
--
作者：
Gobec, S;Brozic, P;Rizner, TL
非甾体抗炎药（NSAIDs），如吲哚美辛、氟芬那酸和相关化合物，最近被确定为AKR1C3的有效抑制剂。我们报道了其他一些非甾体抗炎药（双氯芬酸和萘普生）也能抑制AKR1C3， IC50值在低微摩尔范围内。为了获得更多的结构活性关系信息和寻找新的线索，我们在AKR1C3上合成并筛选了一系列基于NSAIDs设计的化合物。活性最高的化合物为2-[（2,2-二苯乙酰基）氨基]苯甲酸4 （IC50 = 11 μ M）和3-苯氧苯甲酸10 （IC50 = 0.68 μ M）。这些化合物代表了开发新的抗癌药物的有希望的起点。(c) 2005 Elsevier Ltd版权所有。
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 IC50 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 (IC50 = 11 mu M) and 3-phenoxybenzoic acid 10 (IC50 = 0.68 mu M). These compounds represent promising starting points for the development of new anticancer agents. (c) 2005 Elsevier Ltd. All rights reserved.