title: Structure-specific adipogenic capacity of novel, well-defined ternary Zn(II)-Schiff base materials. Biomolecular correlations in zinc-induced differentiation of 3T3-L1 pre-adipocytes to adipocytes.
abstract: Among the various roles of zinc discovered to date, its exogenous activity as an insulin mimetic agent stands as a contemporary challenge currently under investigation and a goal to pursue in the form of a metallodrug against type 2 Diabetes Mellitus. Poised to investigate the adipogenic potential of Zn(II) and appropriately configure its coordination sphere into well-defined anti-diabetic forms, (a) a series of new well-defined ternary dinuclear Zn(II)-L (L=Schiff base ligands with a variable number of alcoholic moieties) compounds were synthesized and physicochemically characterized, (b) their cytotoxicity and migration effect(s) in both pre- and mature adipocytes were assessed, (c) their ability to effectively induce cell differentiation of 3T3-L1 pre-adipocytes into mature adipocytes was established, and (d) closely linked molecular targets involving or influenced by the specific Zn(II) forms were perused through molecular biological techniques, cumulatively delineating factors involved in Zn(II)-induced adipogenesis. Collectively, the results (a) reveal the significance of key structural features of Schiff ligands coordinated to Zn(II), thereby influencing its (a)toxicity behavior and insulin-like activity, (b) project molecular targets influenced by the specific forms of Zn(II) formulating its adipogenic potential, and (c) exemplify the interwoven relationship between Zn(II)-L structural speciation and insulin mimetic biological activity, thereby suggesting ways of fine tuning structure-specific zinc-induced adipogenicity in future efficient antidiabetic drugs.
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: O
authors.initials: O
authors.lastname: Tsave
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Halevas
authors.affiliation: Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: M P
authors.initials: MP
authors.lastname: Yavropoulou
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Kosmidis Papadimitriou
authors.affiliation: Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: J G
authors.initials: JG
authors.lastname: Yovos
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Hatzidimitriou
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Gabriel
authors.affiliation: Institute of Advanced Materials, Physicochemical Processes, Nanotechnology and Microsystems, Department of Materials Science, N.C.S.R. "Demokritos", Aghia Paraskevi 15310, Attiki, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Psycharis
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: salif@auth.gr.
authors.forename: A
authors.initials: A
authors.lastname: Salifoglou
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D051379:Mice; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012545:Schiff Bases / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D012545:Schiff Bases; D015032:Zinc
keywords: Biomolecular correlations; Fine-tuning zinc insulin-like activity; Schiff ligand-based zinc reactivity; Structure-specific bioactivity selection; Zinc metallodrugs; Zinc-induced adipogenesis