Ceborska Magdalena, Siklitskaya Aleksandra, Kowalska Aneta Aniela, Kędra Karolina
Faculty of Mathematics and Natural Sciences, Cardinal Stefan Wyszyński University, Wóycickiego 1/3, 01-938 Warsaw, Poland.
Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
Pharmaceutics. 2024 Sep 3;16(9):1161. doi: 10.3390/pharmaceutics16091161.
Folic acid (FA) and its structural analog, anticancer medicine methotrexate (MTX), are known to form host/guest complexes with native cyclodextrins, of which the most stable are formed with the medium-sized β-cyclodextrin. Based on our research, proving that simple sugars (D-glucose, D-galactose, and D-mannose) can form adducts with folic acid, we envisioned that combining these two types of molecular receptors (cyclodextrin and simple carbohydrates) into one may be beneficial for the complexation of FA and MTX. We designed and obtained host/guest inclusion complexes of FA and MTX with two monoderivatives of β-cyclodextrin-substituted at position 6 with monosaccharide (glucose, G-β-CD) and disaccharide (maltose, Ma-β-CD). The complexation was proved by experimental (NMR, UV-vis, IR, TG, DSC) and theoretical methods. We proved that derivatization of β-cyclodextrin with glucose and maltose has a significant impact on the complexation with FA and MTX, as the addition of one glucose subunit to the structure of the receptor significantly increases the value of association constant for both FA/G-β-CD and MTX/G-β-CD, while further extending a pendant chain (incorporation of maltose subunit) results in no additional changes.
叶酸（FA）及其结构类似物、抗癌药物甲氨蝶呤（MTX），已知可与天然环糊精形成主/客体复合物，其中与中等大小的β-环糊精形成的复合物最稳定。基于我们的研究，已证明单糖（D-葡萄糖、D-半乳糖和D-甘露糖）可与叶酸形成加合物，我们设想将这两种分子受体（环糊精和单糖）结合为一体可能有利于叶酸和甲氨蝶呤的络合。我们设计并获得了叶酸和甲氨蝶呤与β-环糊精的两种单衍生物的主/客体包合物，这两种衍生物在6位被单糖（葡萄糖，G-β-CD）和二糖（麦芽糖，Ma-β-CD）取代。通过实验（核磁共振、紫外可见光谱、红外光谱、热重分析、差示扫描量热法）和理论方法证明了络合作用。我们证明，用葡萄糖和麦芽糖对β-环糊精进行衍生化对与叶酸和甲氨蝶呤的络合有显著影响，因为在受体结构中添加一个葡萄糖亚基会显著增加叶酸/G-β-CD和甲氨蝶呤/G-β-CD的缔合常数，而进一步延长侧链（引入麦芽糖亚基）不会导致额外变化。
