title: Modulation of cell proliferation in rat liver cell cultures by new calix[4]arenes.
abstract: Cell cycle progression is dependent on 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 two aspartic/glutamic acid, ornithine groups or hydrazide function at the lower rim, designed as potential iron chelators. The synthesis only afforded calix[4]arenes in the cone conformation. 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 rat hepatoma cell line Fao by measuring mitochondrial succinate dehydrogenase activity. Their cytotoxicity was evaluated by extracellular LDH activity. Preliminary results indicated that among all tested compounds, monohydrazidocalix[4]arene 2 which is not cytotoxic in Fao cells exhibits interesting antiproliferative activity. This effect, independent on iron depletion, remains to be further explored. Moreover, it also shows that new substituted calix[4]arenes could open the way to new valuable medicinal chemistry scaffolding.
authors.affiliation: EA 3901, DMAG, UFR de Pharmacie et de Médecine, Université de Picardie Jules Verne, 1 rue des Louvels, 80037 Amiens, France.
authors.forename: Viviane Silva
authors.initials: VS
authors.lastname: Pires
authors.forename: Francois
authors.initials: F
authors.lastname: Gaboriau
authors.forename: Jean
authors.initials: J
authors.lastname: Guillon
authors.forename: Sophie
authors.initials: S
authors.lastname: Nascimento
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dassonville
authors.forename: Gerard
authors.initials: G
authors.lastname: Lescoat
authors.forename: Vanessa
authors.initials: V
authors.lastname: Desplat
authors.forename: Jacques
authors.initials: J
authors.lastname: Rochette
authors.forename: Christian
authors.initials: C
authors.lastname: Jarry
authors.forename: Pascal
authors.initials: P
authors.lastname: Sonnet
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D047250:Calixarenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000077588:Deferasirox; D004354:Drug Screening Assays, Antitumor; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors / Q000378:metabolism; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D010636:Phenols; D014230:Triazoles; C121325:calix(4)arene; D047250:Calixarenes; D017665:Hydroxyl Radical; D000077588:Deferasirox