Faculty of Science, Charles University, 128 43 Prague, Czech Republic.
Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, 166 10 Prague, Czech Republic.
Molecules. 2021 Aug 25;26(17):5160. doi: 10.3390/molecules26175160.
Amine-containing drugs often show poor pharmacological properties, but these disadvantages can be overcome by using a prodrug approach involving self-immolative linkers. Accordingly, we designed l-lactate linkers as ideal candidates for amine delivery. Furthermore, we designed linkers bearing two different cargos (aniline and phenol) for preferential amine cargo release within 15 min. Since the linkers carrying secondary amine cargo showed high stability at physiological pH, we used our strategy to prepare phosphate-based prodrugs of the antibiotic Ciprofloxacin. Therefore, our study will facilitate the rational design of new and more effective drug delivery systems for amine-containing drugs.
含胺药物通常表现出较差的药理性质，但这些缺点可以通过使用前药方法克服，该方法涉及自毁性连接物。因此，我们设计了 l-乳酸连接物作为胺类药物递送的理想候选物。此外，我们设计了带有两种不同有效载荷（苯胺和苯酚）的连接物，以在 15 分钟内优先释放胺类有效载荷。由于携带仲胺有效载荷的连接物在生理 pH 值下表现出高稳定性，我们使用该策略制备了抗生素环丙沙星的磷酸盐前药。因此，我们的研究将有助于合理设计新型、更有效的含胺药物给药系统。
