摘要
Androgens’ metabolism and activity are gaining a more and more important role in human physiology particularly referring to aging and to neurodegenerative diseases. Androgen treatment is often required for long-lasting disorders. In order to improve their duration and effects, androgens can be administered as esters of carboxylic acids. The novelty of our research is the use of esters of androgens with specific unsaturated fatty acids, in order to reduce possible side effects particularly related to chronic pathologies with altered lipid homeostasis such as X-linked adrenoleukodystrophy and cardiovascular disorders. Thus the esters of the main androgenic substances testosterone, dihydrotestosterone (DHT) and their metabolite 5α-androstan-3α,17β-diol were chemically obtained by coupling with different unsaturated fatty acids. To this aim, fatty acids with various degree of unsaturation and belonging to different series were selected. Specifically, oleic acid (18:1, n-9), linoleic acid (18:2, n-6), and the n-3 fatty acids, α-linolenic acid (18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) were used obtaining corresponding esters with acceptable yields and good degree of purity. All the synthesized compounds were tested for their cytotoxic activities in mouse NIH3T3 and human astrocyte cell lines. The esters demonstrated good tolerability and no in vitro cytotoxic effect in both cell cultures. After these promising preliminary results, the esters will be suitable for in vivo studies in order to ascertain their pharmacokinetic characteristics and their biological effects. Key-wordsAndrogens DHT testosterone 3alpha-diol unsaturated fatty acids
摘要译文
雄激素鈥代谢和活动正在获得在人体生理学一个越来越重要的作用特别参照老化和神经变性疾病雄激素治疗经常需要持久disordersIn为了提高它们的持续时间和效果，雄激素可以施用作为羧酸的酯我们研究的新颖之处在于使用具有特定的不饱和脂肪酸的雄激素的酯，为了减少可能的副作用特别是与慢性病症具有改变脂质稳态如X-连锁的肾上腺脑白质和心血管疾病从而主雄性物质睾酮，二氢睾酮（DHT）的酯和它们的代谢物5α雄甾3α，17尾二醇进行化学通过用不同的不饱和脂肪酸acidsTo这个目的，脂肪酸与各种不饱和度的耦合和属于不同系列获得的被选择具体地，油酸（18：1，N-9），亚油酸（18：2，N-6），和n-3脂肪酸，α亚麻酸（18：3），二十碳五烯酸（EPA，20 ：5），和二十二碳六烯酸（DHA，22：6）被用于获得具有可接受的产率和好的纯度相应的酯所有合成的化合物在小鼠NIH3T3和人星形胶质细胞系的细胞毒活性测试该酯表现出良好的耐受性和culturesAfter这些有前途的初步结果在两种细胞无体外细胞毒作用，酯将适合于在体内研究，以确定它们的药代动力学特征和它们的生物效应关键wordsAndrogens睾酮DHT 3ALPHA二醇不饱和脂肪酸
F. Aiello [1] A. Garofalo [1] A. M. Aloisi [2] S. Lamponi [3] A. Magnani [3] A. Petroni [4]. Synthesis of esters of androgens with unsaturated fatty acids for androgen requiring therapy[J]. Journal of Endocrinological Investigation, 2013,36(6): 390-395