Faculty of Industrial Chemistry and Environmental Engineering, University Politehnica Timișoara, C. Telbisz 6, 300001 Timișoara, Romania.
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117 Budapest, Hungary.
Int J Mol Sci. 2022 Jul 22;23(15):8103. doi: 10.3390/ijms23158103.
Anthocyanidins, the aglycons of anthocyanins, are known, beyond their function in plants, also as compounds with a wide range of biological and pharmacological activities, including cytostatic effect against various cancer cells. The nature and position of the substituents in the flavylium cation is essential for such biological properties, as well as the equilibrium between the multistate of the different chemical species that are generated by the flavylium cation, including quinoidal base, hemiketal, and - and -chalcones. In this work, eight new flavylium derivatives were synthesized, characterized for confirmation of the structure by FT-IR and 2D-NMR, and investigated in vitro as possible cytostatic compounds against HCT116 and HepG2 cancer cells. The most active two compounds were explored for their halochromic properties that can influence the biological activity and subjected to molecular encapsulation in β-cyclodextrin derivatives in order to increase their solubility in water and bioavailability. The anticancer effect was influenced by the position (6-, 7-, or 8-) of the methoxy group in the β-ring of the methoxy-4'-hydroxy-3'-methoxyflavylium cation, while the study of the halochromic properties revealed the important role played by the chalcone species of the pH-dependent multistate in both the uncomplexed and inclusion complex forms of these anthocyanidins.
花色苷元是花色苷的糖苷配基，除了在植物中的功能外，还已知具有广泛的生物和药理活性，包括对各种癌细胞的细胞抑制作用。在花青阳离子中，取代基的性质和位置对于这种生物特性至关重要，以及由花青阳离子生成的不同化学物质的多态平衡也是如此，包括醌式碱、半缩酮和 - 和 -查耳酮。在这项工作中，合成了八个新的花青衍生物，通过傅里叶变换红外光谱（FT-IR）和二维核磁共振（2D-NMR）进行结构确证，并在体外作为可能的细胞抑制剂对 HCT116 和 HepG2 癌细胞进行了研究。对最活跃的两种化合物进行了变色性质的研究，这些性质可能会影响生物活性，并将其进行分子包封在β-环糊精衍生物中，以增加其在水中的溶解度和生物利用度。抗癌作用受β-环中 7-位或 8-位甲氧基取代基位置的影响（6-、7-、或 8-）甲氧基-4'-羟基-3'-甲氧基花青阳离子，而对变色性质的研究揭示了 pH 依赖性多态性中的查耳酮物种在这些花色苷的未络合和包合形式中所起的重要作用。
