V(v)-Schiff base species induce adipogenesis through structure-specific influence of genetic targets†
Vanadium has been known to exhibit numerous functions in biological systems, projecting exogenous activity linked to regulatory roles in cell metabolism and insulin mimesis. Poised to probe into the vanadium adipogenic potential, reflecting on efficient anti-diabetic drugs, research was launched in our labs to pursue the (a) synthesis of diversely structured Schiff base ligands, as vanadium chelating binders, containing a variably configured o-vanillin core with a specified common organic o-aminophenol tether, (b) synthesis of a family of well-defined soluble vanadium-Schiff base compounds, bearing the above mentioned Schiff ligands (and in one case 4,4′-bipyridine), (c) study of their toxicity profile and adipogenic activity in 3T3-L1 fibroblasts toward mature adipocytes, and (d) determination of molecular biological targets linked to the vanadium-induced cell differentiation process, thereby unravelling factors impacting signaling pathways influencing insulin mimesis. The results suggest that (a) all emerging vanadospecies contain V(V) mononuclear centers bound to Schiff bases (and 4,4′-bipyridine), (b) a well-defined (solid-state and solution) physicochemical profile of all species justifies their selection in biological studies, (c) the vanadium toxicity profile is strongly related to the form of V(V) (complexed forms, substrate-ligand nature), (d) there is a structure-specific behavior of vanadium influencing adipogenesis, and (e) molecular target loci are also influenced by vanadoforms in a structure-specific fashion, thereby collectively projecting an interwoven role of factors emanating from vanadium and impacting cell differentiation and insulin mimetic activity. The so far accrued knowledge constitutes the basis for further development of biomarker-driven structure-specific vanadodrugs, contributing through insulin biomimicry to therapeutic technologies in Diabetes mellitus.
- This article is part of the themed collection: Vanadium Science: Chemistry, Catalysis, Materials, Biological and Medicinal Studies