Bis(6-ethylpicolinato)oxovanadium(IV) complex with normoglycemic activity in KK-Ay mice

Sasagawa, Takahiro; Yoshikawa, Yutaka; Kawabe, Kenji; Sakurai, Hiromu; Kojima, Yoshitane

doi:10.1016/s0162-0134(01)00342-7

Cited by 44 publications

(39 citation statements)

References 16 publications

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“…For the syntheses of the 5-carboalkoxypicolinic acids, 5 ROpicH (1 a ± d), the pyridine-2,5-dicarboxylic acids were converted to the dialkylesters according to known procedures. [14] Reaction with copper(ii) nitrate yielded blue copper complexes, from which the monoesters were liberated with hydrogen sulphide. [15] In the case of 1 a, 1 b and 1 c single crystals were grown out of aqueous acetone.…”

Section: Resultsmentioning

confidence: 99%

“…[13] Synthesis of the monoesters was carried out according to Ooi and Magee, [14] with the modification that a molar ratio diester to copper(ii)nitrate of 1:1 was chosen and the reaction mixture kept at reflux for 3 h to yield the blue copper complexes [Cu(5 ROpic) 2 ], from which the ligands were liberated with H 2 S. The ligands were isolated as white or slightly yellow solids in yields of 44 to 72 %. …”

Section: Syntheses Of Compoundsmentioning

confidence: 99%

“…[9] Starting from these results, various V IV and V V compounds with picH and derivatives of picH were the subject of research activities in terms of their insulin-mimetic (normoglycemic) activity. Examples are complexes with picolineamides, [10] and picolinates with the substituents 5-I, [11] 6-Me, 6-COO À (dipic), [10,12,13] 6-Et [14,15] and 4-OH-dipic. [16,17] It is noteworthy that the oxidation state of vanadium does not seem to play a crucial role in activity.…”

Section: Introductionmentioning

confidence: 99%

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A New Family of Insulin‐Mimetic Vanadium Complexes Derived from 5‐Carboalkoxypicolinates

Gätjens¹,

Meier²,

Kiss³

et al. 2003

Chemistry A European J

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The reaction of 5-carboalkoxypicolinic acid (5 ROpicH, R=Me, Et, iPr, sBu; 1 a-d) with vanadyl sulfate yielded the complexes [VO(H(2)O)(5 ROpic)(2)], 2 a-d, with H(2)O and one of the picolinato ligands in the equatorial positions, and the second picolinate occupying equatorial (N) and axial (O) positions. Reaction of 1 a with [NH(4)][VO(3)] yielded [NH(4)][VO(2)(5 MeOpic)(2)], [NH(4)]-3, in which the N functions of the picolinates are trans to the doubly bonded, cis-positioned oxo groups. Complexes 1 a.H(2)O, 1 b, 1 c, 2 a.3.5 H(2)O and [NH(4)]-3.4 H(2)O have been structurally characterised. A detailed pH-potentiometric solution speciation analysis of the system VO(2+)-1 a revealed a dominance of VO(5 OMepic)(2) between pH 2 and 6, with the same coordination pattern, evidenced by EPR spectroscopy, as in the crystalline solid state. In ternary systems containing physiological concentrations of the low molecular mass biogenic binders (B) lactate, oxalate, citrate or phosphate, ternary species of general composition VO(5 MeOpic)B dominate at physiological pH, with citrate being the most effective competitor for picolinate. All of the complexes trigger glucose uptake and degradation by simian virus modified mice fibroblasts at non-toxic concentrations (<100 microM), with 2 a, [VO(2)(pic)(2)](-) and [VO(2)(dipic)](-) being at least as effective as insulin. Vanadium uptake by the cells is most effective in the case of 2 a. 2 a also effectively inhibits free fatty acid release by rat adipocytes treated with epinephrine, thus mimicking the inhibition of lipolysis by insulin.

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Section: Resultsmentioning

confidence: 99%

Section: Syntheses Of Compoundsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A New Family of Insulin‐Mimetic Vanadium Complexes Derived from 5‐Carboalkoxypicolinates

Gätjens¹,

Meier²,

Kiss³

et al. 2003

Chemistry A European J

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“…The only species characterized by X-ray diffraction analysis with an axially bound water which can be used as a comparison for the octahedral complexes is that formed by 6-ethylpicolinic acid, which however possesses a carboxylate rather than an alcoholate group bound to vanadium. [41] The comparison between [VO(2-HMPH -1 ) 2 ], [VO(2-mentholpyridineH -1 ) 2 ], [39] and [VO(9-(2-pyridyl)fluoren-9-olato) 2 ]·0.5CH 2 Cl 2 [40] shows that the agreement is very good both for the distances and, mainly, for the bond angles: inwww.eurjic.org Table 5 The results demonstrate that with DFT methods it is also possible to calculate well the bond angle between the oxo group and the axial water molecule, which is 179.0 for trans-[VO(2-HMPH -1 ) 2 (H 2 O)] and 177.0°for trans-[VO(6-ethylpicolinato) 2 (H 2 O)]. [41] By going from the pentacoordinate structure of [VO(2-HMPH -1 ) 2 ] to the hexacoordinate structure of trans-[VO(2-HMPH -1 ) 2 (H 2 O)] the bond lengths remain almost unchanged (differences below 1.6 %); concerning the bond angles, N-V-N does not change significantly (from 152.1 to 153.8°), and the only structural parameter that undergoes an important deformation is the O-V-O angle (from 131.9 to 150.8°).…”

Section: Optimization Of the V Iv O Structuresmentioning

confidence: 99%

Potentiometric, Spectroscopic and DFT Study of the V^IVO Complexes Formed by Di(pyridin‐2‐yl) Ligands

Pisano¹,

Kiss²,

Várnagy³

et al. 2009

Eur J Inorg Chem

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The coordinating properties of a series of di(pyridin-2-yl) derivatives towards the V IV O 2+ ion have been studied through the combined application of potentiometric and spectroscopic (electronic absorption and EPR spectroscopies) methods. In particular, di(pyridin-2-yl)amine (DPA), di(pyridin-2-yl)methane (DPM), di(pyridin-2-yl) ketone (DPK), di(pyridin-2-yl)methanol (DPMO), 2-acetylpyridine (2-AP) and 2-hydroxymethylpyridine (2-HMP), and two amino acid derivatives of di(pyridin-2-yl)methylamine (DPMA), namely N-glycyl-DPMA and N-histidyl-DPMA, have been examined. The stability constants of proton and V IV O complexes (logβ) were measured at 25°C and at a constant ionic strength of 0.2 M (KCl). The results show that the simple di(pyridin-2-yl) derivatives having only pyridine nitrogen atoms form mono-chelated species with the (N pyr , N pyr ) donor set, whereas those

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“…1), with particular emphasis on the efficacy of bis(picolinato) oxovanadium(IV) [VO(pa) 2 ] and bis(maltolato)oxovanadium(IV) [VO(mal) 2 ] complexes [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. These two complexes have advantages for examining the structure-activity relationship by adding suitable substituents on the picolinate [20][21][22][23][24][25][26][27][28][29][30] and 3-hydroxypyrone [31][32][33][34] as leading ligands, respectively. Among them, the complexes bis(6-methylpicolinato)oxovanadium(IV) [VO(6mpa) 2 ] and bis(allixinato)oxovanadium(IV) [VO(alx) 2 ] are expected to be especially applicable to clinical use.…”

Section: Introductionmentioning

confidence: 99%

New developments of insulinomimetic dinuclear vanadyl(IV)-tartrate complexes

Funakoshi

Adachi

2005

Pure and Applied Chemistry

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Abstract:The number of patients suffering from diabetes mellitus (DM) is increasing year by year throughout the world. In 2003, the world population was 6.3 billion, and the number of patients with DM in the adult population (20-79 years old) was 0.194 billion, which corresponded to 5.1 % of all disease incidence in that age range. In 2005, it is forecasted that the world population will increase to 8.0 billion and the ratio of DM to total disease incidence will increase to 6.3 %, with a disproportionate number of cases in Southeast Asia, the West Pacific, Central Asia, and North, Central, and South America. To treat Type 1 and Type 2 DM clinically, insulin preparations and synthetic drugs, respectively, have been used. However, these treatments are associated with some problems, such as several times of daily insulin injections following blood glucose monitoring and side effects in the case of the synthetic drugs. Consequently, a new class of therapeutic compounds is anticipated. After many trials, vanadium-containing complexes have been proposed to improve and treat both types of DM by in vivo experiments. We present an overview of insulinomimetic and antidiabetic vanadyl (+4 vanadium, V) complexes, and propose new candidates for dinuclear vanadyl complexes with naturally occurring ligands. The current state of research on the dinuclear vanadyl(IV)-tartrate complexes is described in regard to the physicochemical characteristics, in vitro insulinomimetic and in vivo blood-glucose-lowering effects of the prepared complexes.

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Bis(6-ethylpicolinato)oxovanadium(IV) complex with normoglycemic activity in KK-Ay mice

Cited by 44 publications

References 16 publications

A New Family of Insulin‐Mimetic Vanadium Complexes Derived from 5‐Carboalkoxypicolinates

A New Family of Insulin‐Mimetic Vanadium Complexes Derived from 5‐Carboalkoxypicolinates

Potentiometric, Spectroscopic and DFT Study of the V^IVO Complexes Formed by Di(pyridin‐2‐yl) Ligands

New developments of insulinomimetic dinuclear vanadyl(IV)-tartrate complexes

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Bis(6-ethylpicolinato)oxovanadium(IV) complex with normoglycemic activity in KK-Ay mice

Cited by 44 publications

References 16 publications

A New Family of Insulin‐Mimetic Vanadium Complexes Derived from 5‐Carboalkoxypicolinates

A New Family of Insulin‐Mimetic Vanadium Complexes Derived from 5‐Carboalkoxypicolinates

Potentiometric, Spectroscopic and DFT Study of the VIVO Complexes Formed by Di(pyridin‐2‐yl) Ligands

New developments of insulinomimetic dinuclear vanadyl(IV)-tartrate complexes

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Potentiometric, Spectroscopic and DFT Study of the V^IVO Complexes Formed by Di(pyridin‐2‐yl) Ligands