Kristan Katja, Starcević Stefan, Brunskole Mojca, Rizner Tea Lanisnik, Gobec Stanislav
Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Mol Cell Endocrinol. 2006 Mar 27;248(1-2):239-41. doi: 10.1016/j.mce.2005.10.010. Epub 2005 Dec 6.
The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) have important roles in the regulation of steroid hormone actions through their catalysis of the oxidation or reduction of estrogens and androgens at position 17. Dysfunctions of the human 17beta-HSDs have been associated with reproduction disorders, neuronal diseases and the development of hormone-dependent forms of cancers. Therefore, these enzymes represent interesting targets for the development of new drugs. Here we present a series of new cinnamic acid esters and amides that inhibit the oxidative and reductive reaction catalyzed by 17beta-HSD from the fungus Cochliobolus lunatus, a model enzyme of the short-chain dehydrogenase/reductase superfamily. We found that esters of unsubstituted cinnamic acid were better inhibitors than esters of 3,4,5-trimethoxycinnamic acid. Cinnamates were also more potent inhibitors than structurally related cinnamamides. The compounds presented in this paper are potential leads for the development of inhibitors of human 17beta-HSD isoforms, which may prove to have different therapeutic applications.
17β-羟基类固醇脱氢酶（17β-HSDs）通过催化雌激素和雄激素在17位的氧化或还原反应，在甾体激素作用的调节中发挥重要作用。人类17β-HSDs功能异常与生殖紊乱、神经疾病以及激素依赖性癌症的发生发展有关。因此，这些酶是开发新药的有趣靶点。在此，我们展示了一系列新型肉桂酸酯和酰胺，它们能够抑制来自新月弯孢霉的17β-HSD所催化的氧化和还原反应，新月弯孢霉是短链脱氢酶/还原酶超家族的一种模式酶。我们发现未取代肉桂酸的酯类是比3,4,5-三甲氧基肉桂酸的酯类更好的抑制剂。肉桂酸酯也是比结构相关的肉桂酰胺更有效的抑制剂。本文介绍的这些化合物是开发人类17β-HSD同工型抑制剂的潜在先导物，可能具有不同的治疗应用。
