Medicinal chemistry of gold.
In order to determine the mechanism of action of the anti-arthritic gold complexes, it is necessary to understand the physicochemical properties of these complexes and the exchange of ligands which may occur under physiological conditions, since these factors control the cellular uptake and effects of the gold complexes. Present leads to the forms of gold which may be taken up by cells include the metabolism of the injectable complexes to aurocyanide which is quite a potent inhibitor of the oxidative burst of neutrophils and an even more potent inhibitor of the proliferation of lymphocytes. Further metabolism of aurocyanide to Au(III) complexes is also possible. The orally active complex, auranofin, is active in various cellular systems but the relevance of its in vitro actions to its clinical effects is not known, in part, due to its unknown metabolism. A potentially active derivative of auranofin is a presumed metabolite which can be transferred from plasma to red blood cells. If this metabolite is taken up by red blood cells, then it may be taken up by target cells with consequent pharmacological activity.
Graham
G G
GG
School of Physiology and Pharmacology, University of NSW, Kensington, Australia.
Ziegler
J B
JB
Champion
G D
GD
D018501:Antirheumatic Agents / Q000097:blood / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004304:Dosage Forms; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D050607:Organogold Compounds
D018501:Antirheumatic Agents; D004304:Dosage Forms; D050607:Organogold Compounds