A Spectroscopic Study of Interaction of Auricyanide with n-Acetylcysteine

Abstract

Interaction of auricyanide, an important metabolite of anti-arthritic gold-based drug auranofin, was studied in vitro with a pharmacologically active ligand n-acetylcysteine with a view to understand reactivity of gold in vivo. Formation of reduction product aurocyanide occurred through mono- and di-n-acetylcysteine-substituted intermediates. The product and intermediates were identified and monitored spectrophotometrically and by electrospray ionization mass spectrometry. This study suggests successive substitution with n-acetylcysteine through trans effect. At equimolar concentrations of auricyanide and n-acetylcysteine, only mono-substituted mixed-ligand complex was formed. Substitution of the data obtained to various kinetic models suggested that the reaction orders are 0.6 in terms of n-acetylcysteine, 1.5 in terms of auricyanide, and 2 overall. The intermediates detected in this work may help to synthesize more effective and less toxic gold drugs.

The Ca2+-ATPase Inhibition Potential of Gold(I, III) Compounds

“…Thus, it was described that several inorganic compounds and complexes present Ca 2+ -ATPases IC 50 inhibition values globally not so different from the above well-known Ca 2+ -ATPases drugs inhibitors, for example decavanadate (IC 50 = 15 µM), polyoxotungstates (IC 50 = 0.3-200 µM), polyoxovanadates (IC 50 =1 µM), and vanadium complexes such as BMOV (IC 50 = 40 µM), among others [31][32][33][34][35]. In summary, both gold(I) and gold(III) compounds 1-4 are strong inhibitors of the SR Ca 2+ -ATPase, pointing out this enzyme as a putative target for gold compounds with anticancer activity, described as promising agents for the future in medicinal chemistry [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]23,29,[42][43][44].…”

“…Later, the well-known orally active Au(I)-phosphine-thiolate, a dicoordinate complex, also named auranofin, was developed to treat RA in clinical tests [2,5,6]. Aurothiomalate, aurothioglucose, and auro-bis(thiosulfate) are drugs with composition and structure similar to auranofin that have been extensively referred as anticancer agents [7][8][9][10][11][12][13].…”