Design, synthesis and characterization of novel binary V(V)-Schiff base materials linked with insulin-mimetic vanadium-induced differentiation of 3T3-L1 fibroblasts to adipocytes. Structure–function correlations at the molecular level

• Design of Schiff base organic substrates bearing varying number of alcohol moieties
• Synthesis and physicochemical characterization of binary V(V)-Schiff base compounds
• Insulin-mimetic V(V)-induced fibroblast differentiation to mature adipocytes
• Biomarker proof of insulin-like well-defined vanadoform lipogenicity in adipocytes
• Physicochemically formulated selection of V(V) adipogenicity in anti-diabetic drugs

Among the various roles of vanadium in the regulation of intracellular signaling, energy metabolism and insulin mimesis, its exogenous activity stands as a contemporary challenge currently under investigation and a goal to pursue as a metallodrug against Diabetes mellitus II. In this regard, the lipogenic activity of vanadium linked to the development of well-defined anti-diabetic vanadodrugs has been investigated through: a) specifically designing and synthesizing Schiff base organic ligands L, bearing a variable number of terminal alcohols, b) a series of well-defined soluble binary V(V)-L compounds synthesized and physicochemically characterized, c) a study of their cytotoxic effect and establishment of adipogenic activity in 3T3-L1 fibroblasts toward mature adipocytes, and d) biomarker examination of a closely-linked molecular target involving or influenced by the specific V(V) forms, cumulatively delineating factors involved in potential pathways linked to V(V)-induced insulin-like activity. Collectively, the results a) project the importance of specific structural features in Schiff ligands bound to V(V), thereby influencing the emergence of its (a)toxicity and for the first time its insulin-like activity in pre-adipocyte differentiation, b) contribute to the discovery of molecular targets influenced by the specific vanadoforms seeking to induce glucose uptake, and c) indicate an interplay of V(V) structural speciation and cell-differentiation biological activity, thereby gaining insight into vanadium's potential as a future metallodrug in Diabetes mellitus.

Appropriately designed Schiff-bases promote vanadium binding and afford well-defined V(V)-Schiff ligand compounds. Key structural characteristics of V(V)-bound ligands a) formulate a physicochemically-driven selection of biologically-active complex vanadoforms inducing insulin-mimetic fibroblast differentiation to mature adipocytes, and b) transcribe structure-specific biomarker-tagged vanadium adipogenic activity potentiating vanadodrug development in Diabetes mellitus II.Figure optionsDownload as PowerPoint slide