title: Synthesis and antiproliferative activity of aryl- and heteroaryl-hydrazones derived from xanthone carbaldehydes.
abstract: In order to explore the antiproliferative effect associated with the xanthone framework, several arylhydrazonomethyl derivatives were synthesized from various isomeric 1,3-dihydroxyxanthone carbaldehydes. Variation in the position of the aldehydic function led to three sets of compounds, bearing the hydrazonomethyl chain at positions 5, 6 or 7 on the xanthone nucleus, respectively. The antiproliferative effect of the compounds was evaluated in vitro using the MTT colorimetric method against two human cancer cell lines (MCF-7, breast adenocarcinoma, and KB 3.1, squamous cell oral carcinoma) for two time periods (24 h and 72 h). Among the series, four compounds exhibited interesting growth inhibitory effects against both the cell lines, with IC(50) values in the micromolar concentration range. When compared with doxorubicin, the xanthone derivatives showed moderate cytotoxic effects. Surprisingly, unlike doxorubicin, these compounds displayed no significant time-dependent change in the concentration causing 50% inhibitory effect in proliferation. This unusual cytotoxicity profile led to the hypothesis that these molecules could be endowed with a mechanism of action distinct to that of doxorubicin.
authors.affiliation: Laboratoire de Chimie Thérapeutique, EA2962, Faculté de Pharmacie, Université Victor Segalen Bordeaux 2, 146 Rue Léo-Saignat, 33076 Bordeaux Cedex, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Varache-Lembège
authors.forename: Stéphane
authors.initials: S
authors.lastname: Moreau
authors.forename: Stéphane
authors.initials: S
authors.lastname: Larrouture
authors.forename: Danièle
authors.initials: D
authors.lastname: Montaudon
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
authors.forename: Alain
authors.initials: A
authors.lastname: Nuhrich
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared
chemical_list: D000447:Aldehydes; D006835:Hydrazones