Abstract
Type 2 diabetes became an alarming global health issue since the existing drugs do not prevent its progression. Herein, we aimed to synthesize and characterize a family of oxidovanadium(V) complexes with Schiff base ligands derived from L-/D-valine (val) and salicylaldehyde (sal) or o-vanillin (van) as insulin-mimetic agents and to assess their potential anti-diabetic properties. Two new oxidovanadium(V) complexes, [{VVO(R-salval)(H2O)}(μ2-O){VVO(R-salval)}] and [{VVO(R-vanval)(CH3OH)}2(μ2-O)], and their S-enantiomers were synthesized and characterized. The compounds exhibit optical activity as shown by crystallographic and spectroscopic data. The stability, the capacity to bind bovine serum albumin (BSA), the cytotoxicity against human hepatoma cell line, as well as the potential anti-diabetic activity of the four compounds are investigated. The synthesized compounds are stable for up to three hours in physiological conditions and exhibit a high capacity of binding to BSA. Furthermore, the synthesized compounds display cytocompatibility at biologically relevant concentrations, exert anti-diabetic potential and insulin-mimetic activities by inhibiting the α-amylase and protein tyrosine phosphatase activity, and a long-term increase of insulin receptor phosphorylation compared to the insulin hormone. Thus, the in vitro anti-diabetic potential and insulin-mimetic properties of the newly synthesized oxidovanadium(V) compounds, correlated with their cytocompatibility, make them promising candidates for further investigation as anti-diabetic drugs.
Highlights
Introduction iationsThe prevalence of type 2 diabetes has increased alarmingly in recent years, the development of new effective treatment options to increase insulin sensitivity is a challenge for many researchers [1]
This study aims to synthesize and characterize a family of oxidovanadium(V) complexes with Schiff base ligands derived from L-/D-valine and salicylaldehyde or o-vanillin as insulin-mimetic agents and to assess their potential anti-diabetic properties
The reagents used in this study were analytically pure and were purchased from commercial manufacturers. α-Amylase from porcine pancreas, bovine serum albumin (BSA), 3, 5-dinitrosalicylic acid (DNS), D-/L-valine, dimethyl sulfoxide (DMSO), Dulbecco’s modified Eagle’s medium (DMEM), 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES), ethylenediaminetetraacetic acid (EDTA) tetrasodium salt dihydrate, glycerol, 2-mercaptoethanol, salicylaldehyde, sodium orthovanadate (Na3 VV O4 ), sodium chloride, sodium hydroxide, sodium dodecyl sulfate (SDS), p-Nitrophenyl Phosphate, starch, o-vanillin, Tris, VIV OSO4 3H2 O were from SIGMA-Aldrich (Merck KGaA, Darmstadt, Germany)
Summary
The prevalence of type 2 diabetes has increased alarmingly in recent years, the development of new effective treatment options to increase insulin sensitivity is a challenge for many researchers [1]. Type 2 diabetes is characterized by high blood glucose levels as a consequence of defects in the insulin signaling pathway, including the decrease in the phosphorylation of insulin-stimulated receptor tyrosine kinase (INS R) [2]. There are numerous hypoglycemic drugs known, such as insulin analogs, metformin, sulfonylureas, thiazolidinediones, sodium-glucose co-transporter-2 inhibitors, or acarbose, the diabetic disease progresses over time [3]. The development of new drugs to mimic the biological effects of insulin is essential. Therapeutic applications of vanadium and its compounds have been extensively studied since the 1990s [4]. A large number of in vitro and in vivo studies have
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