Assessment of the in vitro toxicity of calixarenes and a metal-seamed calixarene: a chemical pathway for clinical application

Arnab Dawna, Xue Yaoa, Ying Yub, Jianxiong Jiangab* & Harshita Kumari*aa Division of Pharmaceutical Science, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USAb Department of Pharmaceutical Sciences and Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USACONTACT Harshita Kumari kumariha@ucmail.uc.edu;Jianxiong Jiang jjiang18@uthsc.edu Division of Pharmaceutical Science, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USAABSTRACTCalixarenes 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