Vanadium Complexes with Thioanilidine Derivatives of Aminoacids: Inhibition of Human Phosphatases and Cell-Type Specificity in Various Models of Metabolic Disturbances

Abstract

The synthesis and characteristics of the novel ONS-type vanadium(V) complexes with thioanilidine derivatives of aminoacids have been described. They showed inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1 and SHP2) in the submicromolar range and as well as inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxovanadium(IV)(BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070 also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as components of Schiff base ligand, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models, in general. Moreover, the most of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathway in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all above models, including also glucose utilization in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion has put forward explications for the results within the wider scope of the knowledge about vanadium complexes.