title: 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.
authors.affiliation: UMR-CNRS 6219, Laboratoire des glucides, Faculté de Pharmacie, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Rouge
authors.forename: Viviane Silva
authors.initials: VS
authors.lastname: Pires
authors.forename: François
authors.initials: F
authors.lastname: Gaboriau
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dassonville-Klimpt
authors.forename: Jean
authors.initials: J
authors.lastname: Guillon
authors.forename: Sophie Da
authors.initials: SD
authors.lastname: Nascimento
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Leger
authors.forename: Gerard
authors.initials: G
authors.lastname: Lescoat
authors.forename: Pascal
authors.initials: P
authors.lastname: Sonnet
mesh_terms: D001565:Benzoates / Q000494:pharmacology; D047250:Calixarenes / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000077588:Deferasirox; D015195:Drug Design; D006801:Humans; D007501:Iron / Q000378:metabolism / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D010636:Phenols; D014230:Triazoles; C121325:calix(4)arene; D047250:Calixarenes; D007501:Iron; D000077588:Deferasirox