Antiproliferative effect on HepaRG cell cultures of new calix[4]arenes

Abstract

Cell cycle progression is dependent on the intracellular iron level, and chelators lead to iron depletion and decrease cell proliferation. This antiproliferative effect can be inhibited by exogenous iron. In this work, we present the synthesis of new synthetic calix[4]arene podands bearing alkyl acid and alkyl ester groups at the lower rim, designed as potential iron chelators. We report their effect on cell proliferation, in comparison with the new oral chelator ICL670 (4-[3,5-bis-(2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid). The antiproliferative effect of these new compounds was studied in human hepatocarcinoma HepaRG cell cultures using the MTT assay. Their cytotoxicity was evaluated by extracellular LDH activity. Preliminary results indicate that their antiproliferative effect is due to their cytotoxicity. The efficiency of these compounds, comparable to that of ICL670, was independent of iron depletion. This effect remains to be further explored. Moreover, it also shows that novel substituted calix[4]arenes could open the way to new valuable medicinal chemistry scaffolding.

Keywords::

• Calix[4]arene
• hepatocyte
• HepaRG cell line
• iron chelation
• antiproliferative effect

Acknowledgments

The authors thank Novartis Pharma Laboratories (Basel, Switzerland) for supplying ICL670. This work was supported by a grant from the “programme régional de Picardie: TSFer.” One of the authors (P.R.) was the recipient of a grant from the Région Picardie.

Decleration of interest

The authors have no competing interests as defined by Informa Healthcare journals Publishing Group, or other interests that might be perceived to influence the results and/or discussion reported in this paper.