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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.