Division of Natural Products Chemistry, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
Bioorg Med Chem Lett. 2014 Jan 15;24(2):604-8. doi: 10.1016/j.bmcl.2013.12.008. Epub 2013 Dec 9.
In order to develop new drugs for Alzheimer's disease, we prepared 17 fatty acid derivatives with different chain lengths and different numbers and positions of double bonds by using Wittig reaction and stereospecific hydrogenation of triple bonds as key reactions. Among them, (4Z,15Z)-octadecadienoic acid (10) and (23Z,34Z)-heptatriacontadienoic acid (16) showed the most potent neurite outgrowth activities on Aβ(25-35)-treated rat cortical neurons, which activities were comparable to that of a positive control, NGF. Both fatty acids 10 and 16 possess two (Z)-double bonds at the n-3 and n-14 positions, which might be important for the neurite outgrowth activity.
为了开发治疗阿尔茨海默病的新药，我们通过使用维蒂希反应和三键的立体特异性氢化作为关键反应，制备了 17 种具有不同链长和不同双键数目及位置的脂肪酸衍生物。其中，（4Z，15Z）-十八碳二烯酸（10）和（23Z，34Z）-三十七碳二烯酸（16）在 Aβ（25-35）处理的大鼠皮质神经元中表现出最强的神经突生长活性，其活性可与阳性对照物 NGF 相媲美。这两种脂肪酸 10 和 16 在 n-3 和 n-14 位置都具有两个（Z）-双键，这对于神经突生长活性可能很重要。
