Dawn Arnab, Yao Xue, Yu Ying, Jiang Jianxiong, Kumari Harshita
Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA.
Department of Pharmaceutical Sciences and Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA.
Supramol Chem. 2019;31(7):425-431. doi: 10.1080/10610278.2019.1616732. Epub 2019 May 13.
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 insuffcient biocompatibility studies. Our present study represents a systematic investigation of the cytotoxicity associated with -methylresorcin[4]arene, -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 CC 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.
众所周知，杯芳烃能够形成主客体复合物以及具有明确结构的超分子纳米组装体。然而，这些材料与药物部分结合使用的研究仍在探索之中。一个原因是生物相容性研究不足。我们目前的研究系统地调查了与对甲基间苯二酚杯[4]芳烃、对甲基邻苯三酚杯[4]芳烃、对膦酸化杯[8]芳烃以及一种金属缝合杯芳烃 - 铜（II）配合物相关的细胞毒性，使用了人类HEK293和大鼠C6G细胞系以及两种不同的细胞活力测定方法（MTT和CellTiter - Glo）以避免出现物种偏差结果。所有化合物均表现出低至中度的毒性。CC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接相关物作为潜在药物载体和药物修饰剂的地位，还揭示了通过适当化学修饰来微调其毒理学行为的途径。
