Jovanović-Šanta Suzana S, Petri Edward T, Klisurić Olivera R, Szécsi Mihály, Kovačević Radmila, Petrović Julijana A
Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
Department of Biology and Ecology, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 2, 21000 Novi Sad, Serbia.
Steroids. 2015 May;97:45-53. doi: 10.1016/j.steroids.2014.08.026. Epub 2014 Sep 7.
Since many estrogen derivatives exhibit anti-hormone or enzyme inhibition potential, a large number of steroidal derivatives have been synthesised from appropriate precursors, in order to obtain potential therapeutics for the treatment of hormone-dependent cancers. In molecular docking studies, based on X-ray crystallographic analysis, selected D-homo and D-seco estratriene derivatives were predicted to bind strongly to estrogen receptor α (ERα), aromatase and 17,20 lyase, suggesting they could be good starting compounds for antihormonal studies. Test results in vivo suggest that these compounds do not possess estrogenic activity, while some of them showed weak anti-estrogenic properties. In vitro anti-aromatase and anti-lyase assays showed partial inhibition of these two enzymes, while some compounds activated aromatase. Aromatase activators are capable of promoting estrogen synthesis for treatment of pathological conditions caused by estrogen depletion, e.g. osteopenia or osteoporosis.
由于许多雌激素衍生物具有抗激素或酶抑制潜力，人们已从合适的前体合成了大量甾体衍生物，以获得用于治疗激素依赖性癌症的潜在治疗药物。在基于X射线晶体学分析的分子对接研究中，所选的D-高和D-失碳雌三烯衍生物预计会与雌激素受体α（ERα）、芳香化酶和17,20裂解酶强烈结合，表明它们可能是抗激素研究的良好起始化合物。体内试验结果表明，这些化合物不具有雌激素活性，而其中一些显示出较弱的抗雌激素特性。体外抗芳香化酶和抗裂解酶测定表明这两种酶受到部分抑制，而一些化合物激活了芳香化酶。芳香化酶激活剂能够促进雌激素合成，用于治疗由雌激素缺乏引起的病理状况，如骨质减少或骨质疏松症。
