title: Antiproliferative effect on HepaRG cell cultures of new calix[4]arenes. Part II.
abstract: Cell cycle progression is dependent on the intracellular iron level and chelators can 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 some new synthetic calix[4]arene podands bearing diamino-tetraesters, diamino-tetraalcohols, diamino-tetraacid and tetraaryloxypentoxy groups at the lower rim, designed as potential iron chelators. We report their effect on cell proliferation, in comparison with the new oral chelator ICL670A (4-[3,5-bis-(2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid). The antiproliferative effect of these new compounds was studied in the human hepatocarcinoma HepaRG cell cultures using cell nuclei counting after staining with the DNA intercalating fluorescence dye, Hoechst 33342. Their cytotoxicity was evaluated by the extracellular LDH activity. Preliminary results indicated that their antiproliferative effect was mainly due to their cytotoxicity. The efficiency of these compounds, being comparable to that of ICL670, was independent of iron depletion. This effect remains to be further explored. Moreover, it also shows that the new substituted calix[4]arenes could open the way to valuable new approaches for medicinal chemistry scaffolding.
authors.affiliation: INSERM U577, Université de Bordeaux, Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Latxague
authors.forename: François
authors.initials: F
authors.lastname: Gaboriau
authors.forename: Olivier
authors.initials: O
authors.lastname: Chassande
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Leger
authors.forename: Viviane
authors.initials: V
authors.lastname: Pires
authors.forename: Pascal
authors.initials: P
authors.lastname: Rouge
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dassonville-Klimpt
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fardeau
authors.forename: Christian
authors.initials: C
authors.lastname: Jarry
authors.forename: Gerard
authors.initials: G
authors.lastname: Lescoat
authors.forename: Jean
authors.initials: J
authors.lastname: Guillon
authors.forename: Pascal
authors.initials: P
authors.lastname: Sonnet
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047250:Calixarenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000166:cytology; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D010636:Phenols; C121325:calix(4)arene; D047250:Calixarenes