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

Rehder, Dieter and Pessoa, João Costa and Geraldes, Carlos Frederico Gusmao Campos and Castro, Margarida M. and Kabanos, Themistoklis and Kiss, Tamás and Meier, Beate and Micera, Giovanni and Pettersson, Lage and Rangel, Maria and Salifoglou, Athanasios and Turel, Iztok and Wang, Dongren (2002) In vitrostudy of the insulin-mimetic behaviour of vanadium(IV, V) coordination compounds. Journal of Biological Inorganic Chemistry, Vol. 7 (4-5), p. 384-396. eISSN 1432-1327. Article.

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DOI: 10.1007/s00775-001-0311-5

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 ([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 thanoth ers. Generally, ON ligationis 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 speciationres ults. 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.

Item Type:Article
ID Code:1418
Status:Published
Refereed:Yes
Uncontrolled Keywords:Vanadium compounds, toxicity, insulin mimesis, cell culture tests, solution speciation
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01 Dipartimenti > Chimica
Publisher:Springer Berlin / Heildelberg
eISSN:1432-1327
Copyright Holders:© SBIC 2001
Deposited On:18 Aug 2009 10:05

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