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Vanadium Complexes with Thioanilide Derivatives of Amino Acids: Inhibition of Human Phosphatases and Specificity in Various Cell Models of Metabolic Disturbances.

Grzegorz KazekMonika Głuch-LutwinBarbara MordylElżbieta MenaszekMonika KubackaAnna JurowskaDariusz CieżBartosz TrzewikJanusz SzklarzewiczMonika A Papież
Published in: Pharmaceuticals (Basel, Switzerland) (2024)
In the text, the synthesis and characteristics of the novel ONS-type vanadium (V) complexes with thioanilide derivatives of amino acids are described. They showed the inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1, and SHP2) in the submicromolar range, as well as the inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxidovanadium(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 Schiff base ligand components, 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 majority of the active complexes from both groups showed better effects than VOSO 4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, including also glucose utilizatiand ONO Complexes are Inhibitors ofon in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.
Keyphrases
  • signaling pathway
  • endothelial cells
  • amino acid
  • cell proliferation
  • single cell
  • adipose tissue
  • bone marrow
  • cell cycle
  • cell death
  • ionic liquid
  • molecular docking
  • endoplasmic reticulum stress