Productos Naturales Marinos, Departamento de Farmacia , Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Medellín, Colombia.
Instituto de Física, Universidad de Antioquia, UdeA, Medellín, Colombia.
J Pharm Pharmacol. 2019 Mar;71(3):329-337. doi: 10.1111/jphp.13038. Epub 2018 Nov 20.
Uridine was conjugated with fatty acids to improve the drug lipophilicity and the interaction with phospholipid bilayers.
The esterification reaction using carbodiimides compounds as coupling agents and a nucleophilic catalyst allowed us to synthesize tri-acyl ester derivatives of uridine with fatty acids. Analysis of molecular interactions between these tri-acyl ester derivatives and l-α-dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV) - as a mammalian cell membrane model - have been performed by differential scanning calorimetry (DSC).
The DSC thermograms suggest that nucleoside and uridine triacetate softly interact with phospholipidic multilamellar vesicles which are predominantly located between the polar phase, whereas the tri-acyl ester derivatives with fatty acids (myristic and stearic acids) present a strongly interaction with the DMPC bilayer due to the nucleoside and aliphatic chains parts which are oriented towards the polar and lipophilic phases of the phospholipidic bilayer, respectively. However, the effects caused by the tri-myristoyl uridine and tri-stearoyl uridine are different.
We show how the structural changes of uridine modulate the calorimetric behaviour of DMPC shedding light on their affinity with the phospholipidic biomembrane model.
将尿苷与脂肪酸缀合以提高药物的亲脂性并增强与磷脂双层的相互作用。
使用碳二亚胺化合物作为偶联剂和亲核催化剂的酯化反应使我们能够合成尿苷的三酰酯衍生物与脂肪酸。通过差示扫描量热法（DSC）分析这些三酰酯衍生物与 l-α-二月桂酰基磷脂酰胆碱（DMPC）多层囊泡（MLV）之间的分子相互作用 - 作为哺乳动物细胞膜模型。
DSC 热图谱表明，核苷和尿苷三乙酸酯与磷脂多层囊泡柔和相互作用，这些囊泡主要位于极性相之间，而具有脂肪酸（肉豆蔻酸和硬脂酸）的三酰酯衍生物与 DMPC 双层强烈相互作用，这是由于核苷和脂链部分分别朝向磷脂双层的极性相和疏油相。然而，三肉豆蔻酰尿苷和三硬脂酰尿苷引起的影响不同。
我们展示了尿苷的结构变化如何调节 DMPC 的量热行为，从而揭示了它们与磷脂生物膜模型的亲和力。
