In vitro study of the insulin-mimetic behaviour of vanadium(IV, V) coordination compounds

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• 作者：Dieter Rehder ; Jo?o Costa Pessoa ; Carlos F. Geraldes ; Margarida M. Castro ; Themistoklis Kabanos ; Tam¨¢s Kiss ; Beate Meier ; Giovanni Micera ; Lage Pettersson and Maria Rangel ; et al.
• 刊名：Journal of Biological Inorganic Chemistry
• 出版年：2002
• 出版时间：April 2002
• 年：2002
• 卷：7
• 期：4-5
• 页码：384-396
• 全文大小：633 KB

文摘

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 ([H2VO4]-), [VO(acetylacetonate)2], [VO2(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 3H-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. VV compounds tend to be less toxic than VIV 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 For compound 8, the following information is available: details of the structure determination and refinement, description of the structure, and ORTEP view of the molecule (Fig. S1). Also available is the schematic presentation of the MTT test (Fig. S2), as well as additional compounds for which toxicity and insulin-mimetic tests have been carried out.