ABSTRACT Calixarenes are known to form host–guest complexes and supramolecular nanoassemblies with well-defined architectures. However, the use of these materials in conjunction with drug moieties is still under explored. One reason is the insufficient biocompatibility studies. Our present study represents a systematic in vitro investigation of the cytotoxicity associated with C-methylresorcin[4]arene, C-methylpyrogallol[4]arene, p-phosphonated calix[8]arene and a metal-seamed calixarene–copper(II) complex, using human HEK293 and rat C6G cell lines and two different cell viability assays (MTT and CellTiter-Glo) to avoid species-biased results. All compounds showed low to moderate toxicity. The trend in the CC50 values indicated that the suppression of the coordination ability and the presence of phosphonate groups decrease the overall cytotoxicity of the compounds. The results of this study not only establish calixarenes and their immediate families as potential drug carriers and drug modifiers, but also reveal a pathway for fine-tuning their toxicological behaviour by appropriate chemical modification. Graphical Abstract

中文翻译：

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杯芳烃和金属接缝杯芳烃的体外毒性评估：临床应用的化学途径

摘要 众所周知，杯芳烃可以形成具有明确结构的主客体复合物和超分子纳米组件。然而，这些材料与药物部分的结合使用仍在探索中。原因之一是生物相容性研究不足。我们目前的研究代表了与 C-甲基间苯二酚 [4] 芳烃、C-甲基苯并酚 [4] 芳烃、对膦酸杯 [8] 芳烃和金属接缝杯芳烃 - 铜 (II) 配合物相关的细胞毒性的系统体外研究，使用人 HEK293 和大鼠 C6G 细胞系和两种不同的细胞活力测定（MTT 和 CellTiter-Glo）以避免物种偏倚的结果。所有化合物均表现出低至中度毒性。CC50 值的趋势表明配位能力的抑制和膦酸酯基团的存在降低了化合物的整体细胞毒性。这项研究的结果不仅确立了杯芳烃及其直系亲属作为潜在的药物载体和药物修饰剂的地位，而且揭示了通过适当的化学修饰来微调其毒理学行为的途径。图形概要