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.

Oxovanadium (IV) Dipicolinate: Structure Nucleolytic and Anticancer Property

“…The VO (dipic) used may have a lower cytotoxicity to Caco-2 cells (which are originally derived from a human colorectal adenocarcinoma and are developed into a suitable model for the evaluation of intestinal absorption of drugs). Of relevance here is the fact that the IC 50 values of these three vanadium-dipic complexes is similar to those obtained for bis(maltonato)oxovanadium(IV), vanadyl acetylacetonate, and other vanadium (IV, V) complexes [Yang , et al 2004, Rehder, et al 2002. It also seems reasonable to exclude the presence of ethanol solvate (some concentration as complex, i.e.…”

Therapeutic properties of VO(dmpp)2 as assessed by in vitro and in vivo studies in type 2 diabetic GK rats

“…Among the many vanadium compounds reported in the literature, emphasis is given to the bis(matolato)oxidovanadium(IV) (BMOV) [11,14,37] and the similar one bis(ethylmaltolato) oxidovanadium(IV) (BEOV) [25], the only vanadium compounds tested in clinical trials to date, but other compounds like bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), [VO(dmpp) 2 ] [31,33,[36][37][38][39][40][41], bis(picolinato)oxidovanadium(IV) [VO(pic) 2 ] [24,42,43] and bis(allixinato)oxidovanadium(IV) [18,44,45] have also attracted much interest due to the positive results which have been obtained through in vitro and in vivo studies.…”

“…The VO(dmpp) 2 compound has been extensively studied for a structural characterization [30,31] and to investigate its therapeutic properties using adequate cellular models [33,[37][38][39][40]. Recently, it was shown that it is able to restore normal glucose and lipid metabolism in an obese pre-diabetic animal model, the Zucker fatty rats [36].…”

Sarcoplasmic Reticulum Calcium ATPase Is Inhibited by Organic Vanadium Coordination Compounds: Pyridine-2,6-dicarboxylatodioxovanadium(V), BMOV, and an Amavadine Analogue

“…6,[13][14][15][16] Studies have been carried out with simple salts and coordination complexes of vanadium in oxidation states III, IV, 6,13,14,16 and V. 6,15,16 In addition to the animal studies, a range of studies was also carried out in several cellular systems, which probed the activity of specific classes of vanadium compounds and how these compounds act. [17][18][19] In such biological studies, the nature of the active vanadium compound cannot readily be identified, and consideration of chemical and metabolic processing is difficult. 6,15,16 However, various approaches to address this problem have provided some further insight as to the biological activity of these compounds.…”