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2 2019

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Potentiation of adipogenesis and insulinomimetic effects of a novel vanadium complex (N′-[(E)-(5-bromo-2oxophenyl)methylidene]-4methoxybenzohydrazide)oxido(1,10phenanthroline)vanadium(IV) in 3T3-L1 cells

Kazek Grzegorz, Głuch-Lutwin Monika, Mordyl Barbara, Menaszek Elżbieta, Szklarzewicz Janusz, Gryboś Ryszard, Papież Monika

Science, Technology and Innovation

2019

Vol. 4, no. 1

55--62

Recent research on the action of vanadium compounds shows its important effect on adipogenesis processes and adipocyte function. On the basis of previous screening tests in cellular models, the novel vanadium complex (N′-[(E)-(5-bromo-2-oxophenyl)methylidene]4-methoxybenzohydrazide)oxido(1,10-phenanthroline)vanadium(IV) was selected for this study. This complex exhibits potent inhibition of tyrosine phosphatases, and differences in the degree of inhibition were observed particularly for phosphatases. A significant increase in intracellular lipid accumulation and proliferative effect on 3T3-L1 preadipocytes confirmed the ability of this complex to enhance adipogenesis. The insulinomimetic activity of the tested complex was also demonstrated in fully differentiated 3T3-L1 adipocytes, in which glucose utilization was potentiated. The obtained results support the hypothesis that vanadium complexes show promising possibilities for use as new therapeutic strategies for the treatment of type 2 diabetes.

Cell-based screening for identification of novel vanadium complexes with multidirectional activity relative to cells associated with metabolic disorders

Kazek Grzegorz, Głuch-Lutwin Monika, Modryl Barbara, Menaszek Elżbieta, Szklarzewicz Janusz, Gryboś Ryszard, Papież Monika

Science, Technology and Innovation

2019

Vol. 4, no. 1

47--54

In this study, 110 newly synthesized vanadium complexes from different structural groups were screened in three cell-based models representing the main target tissues for anti-diabetic drugs. In glucose utilization in C2C12 myocyte experiments, 93% of vanadium complexes were shown to have equal or greater activity than bis(maltolato)oxovanadium(IV) (BMOV), the methyl analog of bis(ethylmaltolato)oxovanadium(IV) (BEOV) which has been tested in clinical trials. Moreover, 49% and 50% of these complexes were shown to have equal or greater activity than BMOV in lipid accumulation in 3T3-L1 adipocytes and insulin secretion in RINm5F beta cell experiments, respectively. These results were the basis for the selection of compounds for the subsequent steps in the characterization of anti-diabetic properties. This study provides strong support for the application of screening cell-based assays with a phenotypic approach for the discovery of novel anti-diabetic drugs from the vanadium complex class. This is especially desirable due to the multiple and not fully defined mechanisms of action vanadium compounds.