A new halogenated antidiabetic vanadyl complex, bis(5-iodopicolinato)oxovanadium(IV): in vitro and in vivo insulinomimetic evaluations and metallokinetic analysis

Abstract

A new vanadyl complex, bis(5-iodopicolinato)oxovanadium(IV), VO(IPA)2, with a VO(N2O2) coordination mode, was prepared by mixing 5-iodopicolinic acid and VOSO4 at pH 5, with the structure characterized by electronic absorption, IR, and EPR spectra. Introduction of the halogen atom on to the ligand enhanced the in vitro insulinomimetic activity (IC50 = 0.45 mM) compared with that of bis(picolinato)oxovanadium(IV) (IC50 = 0.59 mM). The hyperglycemia of streptozotocin-induced insulin-dependent diabetic rats was normalized when VO(IPA)2 was given by daily intraperitoneal injection. The normoglycemic effect continued for more than 14 days after the end of treatment. To understand the insulinomimetic action of VO(IPA)2, the organ distribution of vanadium and the blood disposition of vanadyl species were investigated. In diabetic rats treated with VO(IPA)2, vanadium was distributed in almost all tissues examined, especially in bone, indicating that the action of vanadium is not peripheral. Vanadyl concentrations in the blood of normal rats given VO(IPA)2 remain significantly higher and longer than those given other complexes because of its slower clearance rate. VO(IPA)2 binds with the membrane of erythrocytes, probably owing to its high hydrophobicity in addition to its binding with serum albumin. The longer residence of vanadyl species shows the higher normoglyceric effects of VO(IPA)2 among three complexes with the VO(N2O2) coordination mode. On the basis of these results, VO(IPA)2 is indicated to be a preferred agent to treat insulin-dependent diabetes mellitus in experimental animals.

Synthesis and characterization of biologically active new Schiff bases containing 3‐functionalized 1,2,4‐triazoles and their zinc(II) complexes: crystal structure of 4‐bromo‐2‐[(E)‐(1H‐1,2,4‐triazol‐3‐ylimino)‐ methyl]phenol

“…Compounds containing triazole moiety have been revealed to exhibit a wide variety of interesting biological properties such as anticancer, [1,2] antifungal, [3 -6] antimicrobial, [7 -9] analgesic, [10] anti-inflammatory, [11 -14] antibacterial, [15 -19] anticonvulsant [20 -22] and antitubercular. [23 -27] Furthermore, they are used as a versatile reagent in the synthesis of heterocyclic compounds and/or as a raw material in drug synthesis [28a -e] (Fig.…”

Some biologically active oxovanadium(IV) complexes of triazole derived Schiff bases: their synthesis, characterization and biological properties

“…Many drug therapies are in practice to address this severe emerging issue. Amongst them, vanadium-based metallotherapy has proved 2,3 to be one of the most effective clinical remedies. Vanadium is an important trace transition metalloelement that exists in variable oxidation states, and many reports prove its insulin mimetic activity 4,5 .…”

Insulin-Mimetic Vanadyl(IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA)-Release in Isolated Rat Adipocytes

“…5,6,27) In 1995, we proposed a new in vitro assay, based on the inhibition of FFA (free fatty acids)-release from isolated rat adipocytes treated with epinephrine (adrenalin), which is simple and convenient compared with the use of RI reagents. 35) By this in vitro assay, we have evaluated some insulin-mimetic activities of vanadyl complexes with different chemical structures and coordination modes such as VO(O 4 ), 36) VO(N 2 O 2 ), [37][38][39][40][41][42][43] VO(S 2 N 2 ), 36) VO(S 2 O 2 ), 44,45) VO(N 3 O), 39) and VO(N 4 ). 28) Our results indicate that the complexes with a strong ability to inhibit FFA-release from adipocytes lowered the high blood glucose levels in type 1 and 2 diabetic animals more effectively than VOSO 4 .…”