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(H2Cys) in methyl alcohol affords a VIII-Cys compound that is formulated as [VIII(Hcys)3].2HCl.2.5H2O 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 VIII atom through an amine nitrogen and a carboxylate oxygen atoms. Solution studies of 1 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, VIVOSO4.5H2O 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. VIVOSO4.5H2O did not show any total antioxidant capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity caused by 1, VIVOSO4.5H2O 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 VIVOSO4.5H2O 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 VIVOSO4.5H2O were examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that 1 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 VIVOSO4.5H2O exhibited metastases.
Papaioannou
Angelos
A
Department of Chemistry, Section of Inorganic and Analytical Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Manos
Manolis
M
Karkabounas
Spiros
S
Liasko
Roman
R
Evangelou
Angelos M
AM
Correia
Isabel
I
Kalfakakou
Vicky
V
Pessoa
João Costa
JC
Kabanos
Themistoklis
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry*; D003545:Cysteine / Q000008:administration & dosage / Q000737:chemistry*; D015394:Molecular Structure; D009369:Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000737:chemistry*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014638:Vanadates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*
D000970:Antineoplastic Agents; D000975:Antioxidants; D014638:Vanadates; D015260:Neprilysin; D003545:Cysteine