Issue 13, 2008

Biologically relevant O,S-donor compounds. Synthesis, molybdenum complexation and xanthine oxidase inhibition

Abstract

Two O,S-donor ligands, hydroxythiopyrone and hydroxythiopyridinone derivatives, were developed and studied, as well as the corresponding O,O-derivatives, with a view to their potential pharmacological applications as xanthine oxidase (XO) inhibitors. The biological assays revealed that the O,S-ligands present high inhibitory activity towards XO (nanomolar order, close to that of the pharmaceutical drug allopurinol), in contrast to the corresponding O,O-analogues. Due to the biomedical relevance of this molybdenum-containing enzyme, the corresponding Mo(VI) complexes were studied both in solution and in the solid state, aimed at identifying the source of the biological properties. The solution studies showed that, in comparison with the O,O-analogues, the Mo(VI) complexes with the O,S-ligands present some stabilization, which is even more pronounced for the reduced Mo(IV) species. The crystal structures of the Mo(VI) complexes with the hydroxythiopyrone revealed good flexibility of the coordination modes, with two structural isomers and two polymorphic forms for a mononuclear and a binuclear species, respectively. These results give some support to mechanistic proposals for the XO inhibition involving the interaction of the thione group with the molybdenum cofactor, thus indicating a role of the sulfur atom in the XO inhibition.

Graphical abstract: Biologically relevant O,S-donor compounds. Synthesis, molybdenum complexation and xanthine oxidase inhibition

Supplementary files

Article information

Article type
Paper
Submitted
08 Nov 2007
Accepted
10 Jan 2008
First published
20 Feb 2008

Dalton Trans., 2008, 1773-1782

Biologically relevant O,S-donor compounds. Synthesis, molybdenum complexation and xanthine oxidase inhibition

S. Chaves, M. Gil, S. Canário, R. Jelic, M. J. Romão, J. Trincão, E. Herdtweck, J. Sousa, C. Diniz, P. Fresco and M. A. Santos, Dalton Trans., 2008, 1773 DOI: 10.1039/B717172B

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