Faculty of Chemistry, University of Warsaw , Pasteura 1, Warsaw, Poland.
J Phys Chem B. 2013 Oct 31;117(43):13444-50. doi: 10.1021/jp4060632. Epub 2013 Oct 18.
The modification of cyclodextrins (CDs) with side chains containing aromatic groups was found to lead to an increase of the stability of the complex with the anticancer drug doxorubicin (Dox). The formation constants evaluated by voltammetry were several orders of magnitude larger than that of the unmodified β-CD ligand. For the CDs with aromatic moieties connected by linkers containing a triazole group, the formation constants of the complexes at pH 5.5 and 7.4 were very different. At lower pH, binding was much weaker as a result of protonation of the triazole moiety in the linker. The drug was then released from the complex. Molecular modeling of the Dox-β-CD system revealed different possible interactions between Dox and β-CD. The observed pH dependence of the complex formation constant can be exploited for drug delivery to the targeted cells. The toxicities of the synthesized complexes and each of the complex components were tested by the MTT assay on two cell lines, the human lung carcinoma and human cervical cancer cell lines.
用含芳基侧链修饰环糊精（CDs）被发现会导致与抗癌药物阿霉素（Dox）的配合物稳定性增加。通过伏安法评估的形成常数比未修饰的β-CD 配体大几个数量级。对于通过含有三唑基团的连接子连接的芳基部分的 CDs，在 pH 5.5 和 7.4 时，配合物的形成常数非常不同。在较低的 pH 值下，由于连接子中三唑部分的质子化，结合变得弱得多。然后，药物从配合物中释放出来。Dox-β-CD 体系的分子建模揭示了 Dox 和 β-CD 之间可能存在的不同相互作用。配合物形成常数的观察到的 pH 依赖性可用于将药物递送到靶细胞。通过 MTT 测定法在两种细胞系（人肺癌和人宫颈癌细胞系）上测试了合成配合物及其各配合物成分的毒性。
