Solid state and solution studies of a vanadium(III)-L-cysteine compound and demonstration of its antimetastatic, antioxidant and inhibition of neutral endopeptidase activities

Reaction of one equivalent of vanadium(III) chloride with three equivalents Of L-cysteine(H(2)Cys) in methyl alcohol affords a V-III-Cys compound that is formulated as [V-III(HCYS)(3)] . 2HCl . 2.5H(2)O 1. The solid state characterization of 1 was performed by microanalysis, circular dichroism (CD) and infrared studies as well as room temperature magnetic susceptibility. These studies have shown coordination of each HCys(-) ligand to the V-III atom through an amine nitrogen and a carboxylate oxygen atoms. Solution studies of I were carried out in water and methanol by UV visible, CD and electron paramagnetic resonance (EPR) spectroscopies. According to these studies, it was evident that despite the progressive oxidation of 1 to oxovanadium(IV) species, some V(III) species were also present in solution after several hours. Compound 1, (VOSO4)-O-IV.5H(2)O and L-cysteine were examined for their total antioxidant capacity (TAC) and lag time. Compound 1 exhibited significantly greater total antioxidant capacity and lag time values than L-cysteine. (VOSO4)-O-IV.5H(2)O did not show any total antioxidant capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity caused by 1, (VOSO4)-O-IV . 5H(2)O and thiorphan was also measured. Compound 1, at a concentration of 10(-3) M, showed inhibition of NEP activity as potent as thiorphan at 10(-6) M, while (VOSO4)-O-IV . 5H(2)O in the same concentration exhibited less than 50% inhibitory activity than that of thiorphan at 10-6 M. Moreover, the antimetastatic effects of compound 1, L-CySteine and (VOSO4)-O-IV . 5H(2)O were examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that I prevents significantly lung metastases (only 9.5% of animals treated with 1 showed metastases), whereas 47-52% of the rats of the control group and those treated with L-cysteine and (VOSO4)-O-IV . 5H(2)O exhibited metastases. (C) 2004 Elsevier Inc. All rights reserved.