Department of Chemistry and Technology of Drugs, "Department of Excellence 2018-2022", Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy.
Center for Life Nano and Neuroscience, Italian Institute of Technology, Viale Regina Elena 291, 00161 Rome, Italy.
Int J Mol Sci. 2021 Oct 29;22(21):11785. doi: 10.3390/ijms222111785.
Many biologically active compounds feature low solubility in aqueous media and, thus, poor bioavailability. The formation of the host-guest complex by using calixarene-based macrocycles (i.e., resorcinol-derived cyclic oligomers) with a good solubility profile can improve solubilization of hydrophobic drugs. Herein, we explore the ability of resorc[4]arenes to self-assemble in polar solutions, to form supramolecular aggregates, and to promote water-solubility of an isoflavone endowed with anti-cancer activity, namely Glabrescione B (GlaB). Accordingly, we synthesized several architectures featuring a different pattern of substitution on the upper rim including functional groups able to undergo acid dissociation (i.e., carboxyl and hydroxyl groups). The aggregation phenomenon of the amphiphilic resorc[4]arenes has been investigated in a THF/water solution by UV-visible spectroscopy, at different pH values. Based on their ionization properties, we demonstrated that the supramolecular assembly of resorc[4]arene-based systems can be modulated at given pH values, and thus promoting the solubility of GlaB.
许多具有生物活性的化合物在水介质中的溶解度较低，因此生物利用度较差。通过使用具有良好溶解度的杯芳烃基大环（即间苯二酚衍生的环状低聚物）形成主客体配合物，可以提高疏水性药物的溶解度。在此，我们探索了杯[4]芳烃在极性溶液中自组装、形成超分子聚集体以及促进具有抗癌活性的异黄酮 Glabrescione B（GlaB）水溶性的能力。相应地，我们合成了几种在上缘具有不同取代模式的结构，包括能够发生酸离解的官能团（即羧基和羟基）。通过紫外-可见光谱在不同 pH 值下研究了两亲性杯[4]芳烃在 THF/水溶液中的聚集现象。基于它们的电离特性，我们证明了基于杯[4]芳烃的体系的超分子组装可以在给定的 pH 值下进行调节，从而提高 GlaB 的溶解度。
