Elsevier

Polyhedron

Volume 27, Issue 6, 25 April 2008, Pages 1787-1794
Polyhedron

Oxovanadium(IV) and (V) complexes of acetylpyridine-derived semicarbazones exhibit insulin-like activity

https://doi.org/10.1016/j.poly.2008.02.014Get rights and content

Abstract

Reaction of 2-acetylpyridine semicarbazone (H2APS), 3-acetylpyridine semicarbazone (H3APS) and 4-acetylpyridine semicarbazone (H4APS) with [VO(acac)2] (acac = acetylacetonate) gave [VO(H2APS)(acac)2] (1), [VO(H3APS)(acac)2] (2) and [VO(4APS)(acac)(H2O)] · 1/2H2O (3). Oxidation of complex 1 in acetonitrile gave [VO2(2APS)] (4). The crystal structures of complexes 1 and 4 have been determined. Complexes 13 were able to enhance glucose uptake and to inhibit glycerol release from adipocytes, which indicate their potential to act as insulin-mimics.

Graphical abstract

Reaction of 2-acetylpyridine (H2APS), 3-acetylpyridine (H3APS) and 4-acetylpyridine semicarbazone (H4APS) with [VO(acac)2] (acac = acetylacetonate) gave [VO(H2APS)(acac)2] (1), [VO(H3APS)(acac)2] (2) and [VO(4APS)(acac)(H2O)] · 1/2H2O (3). Oxidation of complex 1 gave [VO2(2APS)] (4). Complexes 13 were able to enhance glucose uptake and inhibit glycerol release from adipocytes.

  1. Download : Download full-size image

Introduction

Vanadium compounds present innumerous pharmacological applications as antitumorals, antimicrobials and insulin-mimics [1]. It has been demonstrated that the insulin effects of promoting glucose uptake and inhibiting lipolysis can be duplicated by vanadium. Because insulin is a protein it is not orally active. By contrast, vanadium compounds can be orally administered, potentially eliminating or reducing the need for daily insulin injections [2]. In recent years the interest in the insulin-like effects of vanadium has increased, and different approaches have been attempted for the development of new potent vanadium-containing insulin mimic agents [3].

Semicarbazones and their metal complexes exhibit a wide range of bioactivities [4]. Complexes of semicarbazones with a variety of metal ions have been extensively studied but vanadium complexes have received less attention. Vanadium complexes of semicarbazones of low molecular weight could in principle be useful as potential biomimetic drugs.

Several V(IV) complexes with N2O2, N4 and O4 coordination spheres have been proposed as insulin-mimics [5]. In order to study the effects on activity, of different coordination spheres (N–N–O, N–O), in the present work we prepared vanadium(IV) and (V) complexes with 2-, 3-, and 4-acetylpyridine semicarbazone (H2APS, H3APS and H4APS, Fig. 1). The insulin-like effect of the studied compounds has been investigated in vitro in rat adipocytes.

Section snippets

Materials and measurements

All common chemicals were purchased from Aldrich and used without further purification. The semicarbazones were prepared according to standard procedures [6].

Partial elemental analyses were performed on a Perkin–Elmer CHN 2400 analyzer. An YSI model 31 conductivity bridge was employed for molar conductivity measurements. Thermogravimetric curves were obtained with a Mettler TA-4000 equipment. Magnetic susceptibility measurements were carried out on a Johnson Matthey MSB/AUTO balance. UV spectra

Results and discussion

Microanalyses suggest the formation of [VO(H2APS)(acac)2] (1), [VO(H3APS)(acac)2] (2) and of [VO(4APS)(acac)(H2O)] · 1/2H2O (3). In complexes 1 and 2 the semicarbazone acts as a neutral ligand while in 3 the semicarbazone is attached to the metal centre in the anionic (4APS) form. A second product was isolated in the reaction with H2APS, [VO2(2APS)] (4), containing vanadium(V) and an anionic semicarbazone. Complex 4 was also obtained by reacting [VO(acac)2] with H2APS in acetonitrile during 72 h.

Conclusions

The oxovanadium(IV) complexes with 2-, 3- and 4-acetylpyridine semicarbazones were able to enhance glucose uptake and inhibit glycerol release from adipocytes. In complex 4 the ability to promote glucose uptake was lost. Although the vanadyl complexes showed insulin-mimic properties, this effect is not better than that of the starting salt. Further investigation is underway with vanadium complexes of a variety of semicarbazones.

Acknowledgements

This work was supported by Capes, CNPq, Instituto do Milênio – Inovação e Desenvolvimento de Novos Fármacos e Medicamentos (IM-INOFAR) (Proc. CNPq 420015/05-1), and FAPESP of Brazil.

References (26)

  • P. Noblía et al.

    J. Inorg. Biochem.

    (2005)
  • K.H. Thompson et al.

    J. Inorg. Biochem.

    (2006)
  • H. Beraldo et al.

    Spectrochim. Acta

    (2001)
  • M. Rodbell

    J. Biol. Chem.

    (1964)
  • S. Gasic et al.

    Biochem. Pharm.

    (1995)
  • H. Sakurai et al.

    Inorg. Chim. Acta

    (1998)
  • A. Perez-Rebolledo et al.

    J. Mol. Struct.

    (2006)
  • M.R. Maurya

    Coord. Chem. Rev.

    (2003)
  • M.R. Maurya et al.

    Inorg. Chim. Acta

    (2006)
  • M.Z. Mehdi et al.

    Arch. Biochem. Biophys.

    (2005)
  • W. Basuki et al.

    Biochem. Biophys. Res. Commun.

    (2006)
  • B. Lu et al.

    J. Biol. Chem.

    (2001)
  • G. Swarup et al.

    Biochem. Biophys. Res. Commun.

    (1982)
  • Cited by (0)

    View full text