Gobec Stanislav, Brozic Petra, Rizner Tea Lanisnik
Faculty of Pharmacy, University of Ljubljana, Slovenia.
Bioorg Med Chem Lett. 2005 Dec 1;15(23):5170-5. doi: 10.1016/j.bmcl.2005.08.063. Epub 2005 Sep 23.
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.
像吲哚美辛、氟芬那酸及相关化合物这样的非甾体抗炎药（NSAIDs）最近被确定为AKR1C3的强效抑制剂。我们报告称，其他一些NSAIDs（双氯芬酸和萘普生）也能抑制AKR1C3，其半数抑制浓度（IC50）值处于低微摩尔范围内。为了获取更多关于构效关系的信息并确定新的先导化合物，我们合成了一系列基于NSAIDs设计的化合物，并对其进行了AKR1C3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（IC50 = 11微摩尔）和3-苯氧基苯甲酸10（IC50 = 0.68微摩尔）。这些化合物是开发新型抗癌药物的有前景的起点。
