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.
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.
Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
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Halevas
Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
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Tsave
Division of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
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Yavropoulou
Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
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Hatzidimitriou
Division of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
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Yovos
Institute of Advanced Materials, Physicochemical Processes, Nanotechnology and Microsystems, N.C.S.R. "Demokritos", Aghia Paraskevi 15310, Attiki, Greece.
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Psycharis
Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; Center for Research of the Structure of Matter, Magnetic Resonance Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
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Gabriel
Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: salif@auth.gr.
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Salifoglou
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D000818:Animals; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D012545:Schiff Bases / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014639:Vanadium / Q000737:chemistry*
D056831:Coordination Complexes; D012545:Schiff Bases; D014639:Vanadium
Adipogenesis; Binary vanadium-organic ligand metallodrugs; Fine-tuning vanadium bioactivity; Insulin-mimetic activity; Schiff ligand design; Vanadium-induced cellular differentiation