Vávrová Katerina, Zbytovská Jarmila, Palát Karel, Holas Tomás, Klimentová Jana, Hrabálek Alexandr, Dolezal Pavel
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
Eur J Pharm Sci. 2004 Apr;21(5):581-7. doi: 10.1016/j.ejps.2003.12.009.
Stratum corneum ceramides are fundamental for maintaining the skin barrier properties. Their content is decreased in some skin diseases, e.g. atopic dermatitis, and ceramide supplementation is one of the therapeutic approaches. In the present study we have designed novel ceramide analogue 14S24 ((S)-2-tetracosanoylamino-3-hydroxypropionic acid tetradecyl ester) as a potential barrier-repairing agent. We report a convenient two-step synthesis of this analogue with high yields. The ability of 14S24 to repair the disturbed skin barrier was evaluated in vitro on the porcine skin. After 2h application of 14S24 on the skin disrupted by lipid extraction, the permeability decreased significantly almost to the values of the native skin. The compound is effective in 0.1% aqueous suspension and its effect is comparable with physiological skin lipids under the same condition. The comparison of 14S24 and skin ceramides was made via computer modelling and the in silico physico-chemical parameters are reported. We suggest that allylic hydroxyl, that is essential for the apoptogenic activity of ceramides, is not a necessary component of the skin barrier-forming ceramides. The main result of this study is to demonstrate that simpler and easier-to-synthesise ceramide analogues could be effective in the skin barrier repair.
角质层神经酰胺对于维持皮肤屏障特性至关重要。在某些皮肤病（如特应性皮炎）中它们的含量会降低，补充神经酰胺是治疗方法之一。在本研究中，我们设计了新型神经酰胺类似物14S24（(S)-2-二十四烷酰氨基-3-羟基丙酸十四烷基酯）作为一种潜在的屏障修复剂。我们报道了一种简便的两步合成法，该类似物产率高。在猪皮肤上体外评估了14S24修复受损皮肤屏障的能力。在脂质提取破坏的皮肤上涂抹14S24 2小时后，渗透率显著降低，几乎降至正常皮肤的值。该化合物在0.1%的水悬浮液中有效，且在相同条件下其效果与生理性皮肤脂质相当。通过计算机建模对14S24和皮肤神经酰胺进行了比较，并报告了计算机模拟的物理化学参数。我们认为，对于神经酰胺的凋亡活性至关重要的烯丙基羟基并非形成皮肤屏障的神经酰胺的必要成分。本研究的主要结果是证明更简单且易于合成的神经酰胺类似物在皮肤屏障修复中可能有效。
