Novel vanadyl complexes with quinoxaline N1,N4-dioxide derivatives as potent in vitro insulin-mimetic compounds

As a contribution to the development of novel vanadyl complexes with potential insulin-mimetic activity, three new oxovanadium(IV) complexes with the formula VO(L)(2), where L are 3-amino-quinoxaline-2-carbonitrile N-1,N-4-dioxide derivatives, have been synthesized. Complexes have been characterized by elemental and thermal analyses, fast atom bombardment mass spectroscopy (FAB-MS), conductivity measurements and electronic, Fourier transform infrared (FTIR) and electron paramagnetic resonance (EPR) spectroscopies. The in vitro insulin-mimetic activity of the vanadyl complexes has been estimated by lipolysis inhibition tests, in which the inhibition of the release of free fatty acid from isolated rat adipocytes treated with epinephrine was determined. All the complexes showed inhibitory effects on free fatty acid release. [(VO)-O-IV(3-amino-6(7)-bromoquinoxaline-2-carbonitrile N-1,N-4-dioxide)(2)] exhibited higher in vitro insulin-mimetic activity than the very active bis(6-methylpicolinato)oxovanadium(IV), VO(6mpa)(2). This new vanadyl complex is expected to exhibit a higher blood glucose lowering activity than VO(6mpa)(2) in diabetic animals. (C) 2005 Elsevier Inc. All rights reserved.