配方研究与新型NSAID衍生物的循环德克斯特林
Sandra Ramos-Inza1,2, Cristina Morán-Serradilla1, Leire Gaviria-Soteras1
1Department of Pharmaceutical Sciences, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
International journal of molecular sciences
|February 10, 2024
概括
含的NSAID衍生物显示出抗癌潜力,但面临溶解性问题. 循环德克斯 (CD) 复合显著提高了这些化合物的水溶性,有助于它们的制药开发.
科学领域:
- 制药化学 制药化学 制药化学
- 药用化学 医学化学
- 超分子化学 超分子化学
背景情况:
- 环极素 (CDs) 广泛用于通过包容复合物 (IC) 形成来提高药物溶解性,稳定性和生物可用性.
- 含 (Se) 的化合物表现出有前途的抗癌特性,但其临床应用受到水溶性差和不愉快的味道的阻碍.
研究的目的:
- 为了增强含有的非类固醇抗炎药物 (NSAID) 衍生物的水溶性,使用循环德克斯来证明具有抗瘤活性.
- 研究CD和Se-NSAID衍生物之间的相互作用,以克服制药方面的局限性.
主要方法:
- 在各种环极 (CD) 和含有的NSAID衍生物 ( Ester或二二化物形式) 之间形成包含综合体 (IC).
- 使用核磁共振 (NMR) 光谱分析CD复合体.
- 使用分子建模技术构建理论CD化合物复合体的3D模型,以补充实验数据.
主要成果:
- 化合物I.3e和II.5在与CDs复合后显示出水溶性显著增加.
- 增强的溶解性归因于这些特定化合物与CDs之间形成最稳定的相互作用.
- 在 silico 研究证实了实验结果,支持形成的包容性复合物的稳定性.
结论:
- 鉴定出β-cyclodextrin (β-CD) 和gamma-cyclodextrin (γ-CD) 是最适合用于提高所研究的衍生物可溶性的CD.
- CD复杂化是一种可行的策略,可以克服含有的抗癌剂的制药缺点,为进一步的临床评估铺平道路.
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