Zivec Matej, Sova Matej, Brunskole Mojca, Lenarsic Roman, Rizner Tea Lanisnik, Gobec Stanislav
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
J Enzyme Inhib Med Chem. 2007 Feb;22(1):29-36. doi: 10.1080/14756360600953819.
The synthesis and activity of a new series of non-steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase that are based on a 1,5-benzodiazepine scaffold are presented. Their inhibitory potential was screened against 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta-HSDcl), a model enzyme of the short-chain dehydrogenase/reductase superfamily. Some of these compounds are potent inhibitors of 17beta-HSDcl activity, with IC50 values in the low micromolar range and represent promising lead compounds that should be further developed and investigated as inhibitors of human 17beta-HSD isoforms, which are the enzymes associated with the development of many hormone-dependent and neuronal diseases.
本文介绍了一系列基于1,5-苯二氮䓬骨架的新型非甾体17β-羟基类固醇脱氢酶抑制剂的合成及活性。针对来自真菌新月弯孢菌（17β-HSDcl）的17β-羟基类固醇脱氢酶（短链脱氢酶/还原酶超家族的一种模型酶）筛选了它们的抑制潜力。其中一些化合物是17β-HSDcl活性的有效抑制剂，IC50值在低微摩尔范围内，是有前景的先导化合物，应进一步开发并作为人类17β-羟基类固醇脱氢酶同工型的抑制剂进行研究，这些同工型酶与许多激素依赖性和神经疾病的发生有关。
