Cell-based Screening For Identification Of The Novel Vanadium Complexes With Multidirectional Activity Relative To The Cells And The Mechanisms Associated With Metabolic Disorders

Abstract

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.