title: In vitro study of the insulin-mimetic behaviour of vanadium(IV, V) coordination compounds.
abstract: A representative set of vanadium(IV and V) compounds in varying coordination environments has been tested in the concentration range 1 to 10(-6) mM, using transformed mice fibroblasts (cell line SV 3T3), with respect to their short-term cell toxicity (up to 36 hours) and their ability to stimulate glucose uptake by cells. These insulin-mimetic tests have also been carried out with non-transformed human fibroblasts (cell line F26). The compounds under investigation comprise established insulin-mimetic species such as vanadate ([H(2)VO(4)](-)), [VO(acetylacetonate)(2)], [VO(2)(dipicolinate)](-) and [VO(maltolate)(2)], and new systems and coordination compounds containing OO, ON, OS, NS and ONS donor atom sets. A vitality test assay, measuring the reduction equivalents released in the mitochondrial respiratory chain by intracellular glucose degradation, is introduced and the results are counter-checked with (3)H-labelled glucose. Most compounds are toxic at the 1 mM concentration level, and most compounds are essentially non-toxic and about as effective as or more potent than insulin at concentrations of 0.01 mM and below. V(V) compounds tend to be less toxic than V(IV)compounds, and complexes containing thio functional ligands are somewhat more toxic than others. Generally, ON ligation is superior in insulin-mimetic efficacy to OO or O/ NS coordination, irrespective of the vanadium oxidation state. There is, however, no striking correlation between the nature of the ligand systems and the insulin-mimetic potency in these cell culture tests, encompassing 41 vanadium compounds, the results on 22 of which are reported in detail here. The syntheses and characteristics of various new compounds are provided together with selected speciation results. The crystal and molecular structures of [[VO(naph-tris)](2)] [where naph-tris is the Schiff base formed between o-hydroxynaphthaldehyde and tris(hydroxymethyl)amine] are reported. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00775-001-0311-5.
authors.affiliation: Institute of Inorganic and Applied Chemistry, University of Hamburg, 20146 Hamburg, Germany. rehder@xray.chemie.uni-hamburg.de
authors.forename: Dieter
authors.initials: D
authors.lastname: Rehder
authors.forename: João
authors.initials: J
authors.lastname: Costa Pessoa
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
authors.forename: MargaridaM C A
authors.initials: MC
authors.lastname: Castro
authors.forename: Themistoklis
authors.initials: T
authors.lastname: Kabanos
authors.forename: Tamás
authors.initials: T
authors.lastname: Kiss
authors.forename: Beate
authors.initials: B
authors.lastname: Meier
authors.forename: Giovanni
authors.initials: G
authors.lastname: Micera
authors.forename: Lage
authors.initials: L
authors.lastname: Pettersson
authors.forename: Maria
authors.initials: M
authors.lastname: Rangel
authors.forename: Athanasios
authors.initials: A
authors.lastname: Salifoglou
authors.forename: Iztok
authors.initials: I
authors.lastname: Turel
authors.forename: Dongren
authors.initials: D
authors.lastname: Wang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D018716:Molecular Mimicry; D015203:Reproducibility of Results; D018675:Toxicity Tests; D017968:Vanadium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D007328:Insulin; D017968:Vanadium Compounds; D005947:Glucose