调整β-环糊精的结构以改善蒽醌类药物的包合作用。
Adjusting the Structure of β-Cyclodextrin to Improve Complexation of Anthraquinone-Derived Drugs.
机构信息
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02093 Warsaw, Poland.
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02089 Warsaw, Poland.
出版信息
Molecules. 2021 Nov 27;26(23):7205. doi: 10.3390/molecules26237205.
β-Cyclodextrin (CD) derivatives containing an aromatic triazole ring were studied as potential carriers of the following drugs containing an anthraquinone moiety: anthraquinone-2-sulfonic acid (AQ2S); anthraquinone-2-carboxylic acid (AQ2CA); and a common anthracycline, daunorubicin (DNR). UV-Vis and voltammetry measurements were carried out to determine the solubilities and association constants of the complexes formed, and the results revealed the unique properties of the chosen CDs as effective pH-dependent drug complexing agents. The association constants of the drug complexes with the CDs containing a triazole and lipoic acid (βCDLip) or galactosamine (βCDGAL), were significantly larger than that of the native βCD. The AQ2CA and AQ2S drugs were poorly soluble, and their solubilities increased as a result of complex formation with βCDLip and βCDGAL ligands. AQ2CA and AQ2S are negatively charged at pH 7.4. Therefore, they were less prone to form an inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when protonated. The βCDTriazole and βCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at an acidic pH (pH 5.5) than in a neutral medium (pH 7.4) in which the drug dissociates to its neutral, uncharged form. This pH dependence is favorable for antitumor applications.
β-环糊精（CD）衍生物含有一个芳香三唑环，被研究为含有蒽醌部分的以下药物的潜在载体：蒽醌-2-磺酸（AQ2S）；蒽醌-2-羧酸（AQ2CA）；和一种常见的蒽环类药物，柔红霉素（DNR）。进行了 UV-Vis 和伏安法测量，以确定形成的配合物的溶解度和缔合常数，结果表明所选 CD 具有独特的性质，是有效的 pH 依赖性药物络合剂。含三唑和硫辛酸（βCDLip）或半乳糖胺（βCDGAL）的 CD 与药物的缔合常数明显大于天然βCD。AQ2CA 和 AQ2S 药物的溶解度较差，其溶解度由于与βCDLip 和βCDGAL 配体形成配合物而增加。AQ2CA 和 AQ2S 在 pH 7.4 时带负电荷。因此，与带正电荷的 CD 空腔形成包含复合物的倾向不如在 pH 3 时（胃内液体的特征）质子化时那么大。发现βCDTriazole 和βCDGAL 配体在酸性 pH（pH 5.5）下与带正电荷的药物 DNR 形成较弱的包含复合物，而在中性介质（pH 7.4）中药物解离为中性、不带电形式。这种 pH 依赖性有利于抗肿瘤应用。
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