Sud'ina G F, Pushkareva M A, Shephard P, Klein T
A.N. Belozersky Institute of Physico-Chemical Biology of the Moscow State University, Leninskie Gory, Building A, 199991 Moscow, Russian Federation.
Prostaglandins Leukot Essent Fatty Acids. 2008 Feb;78(2):99-108. doi: 10.1016/j.plefa.2007.12.006. Epub 2008 Feb 15.
In vitro evaluations of the selectivity of COX inhibitors are based on a great variety of experimental protocols. As a result, data available on cyclooxygenase (COX)-1/COX-2/5- lipoxygenase (LOX) selectivity of COX inhibitors lack consistency. We, therefore, performed a systematic analysis of the COX-1/COX-2/5-LOX selectivity of 14 compounds with selective COX inhibitory activity (Coxibs). The compounds belonged to different structural classes and were analyzed employing the well-recognized whole-blood assay. 5-LOX activity was also tested on isolated human polymorphonuclear leukocytes. Among COX inhibitors, celecoxib and ML-3000 (licofelone) inhibited 5-LOX in human neutrophils at micromolar ranges. Surprisingly, ML-3000 had no effect on 5-LOX product synthesis in whole-blood assay. In addition, we could show that inhibition of COX pathways did not increase the transformation of arachidonic acid by the 5-LOX pathway.
环氧化酶（COX）抑制剂选择性的体外评估基于各种各样的实验方案。因此，关于COX抑制剂的环氧化酶（COX）-1/COX-2/5-脂氧合酶（LOX）选择性的现有数据缺乏一致性。因此，我们对14种具有选择性COX抑制活性的化合物（昔布类）的COX-1/COX-2/5-LOX选择性进行了系统分析。这些化合物属于不同的结构类别，并采用公认的全血检测法进行分析。还在分离的人多形核白细胞上测试了5-LOX活性。在COX抑制剂中，塞来昔布和ML-3000（利考昔芬）在微摩尔范围内抑制人中性粒细胞中的5-LOX。令人惊讶的是，在全血检测中ML-3000对5-LOX产物合成没有影响。此外，我们可以证明抑制COX途径不会增加5-LOX途径对花生四烯酸的转化。
