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Antimalarial drugs such as chloroquine are beneficial agents in systemic lupus and rheumatoid arthritis. In this work, two new chloroquine diphosphate (CQDP) complexes containing Zn(II) and Au(III) of formula Zn(CQDP)(NO 3 ) 2 (1) and Au(CQDP)Cl 3 (2), respectively, were synthesized and characterized by physico-chemical and spectroscopic methods. To examine their possible antiinflammatory properties, the new derivatives were tested in the range from 1 to 100 lM on the respiratory burst of isolated human neutrophils (PMNs) as well as in whole blood. In isolated PMNs, complex 1 inhibited the isoluminol-enhanced chemiluminescence (IL-CL) only at the highest concentration tested, whereas in the whole blood assay, 10 lM of this complex was sufficient to significantly inhibit the luminolenhanced chemiluminescence (L-CL). On the contrary, complex 2 dose-dependently inhibited the IL-CL but affected the L-CL only at 100 lM. In conclusion, both complexes are more active than CQDP and may be useful for future treatment of diseases resulting from exacerbated neutrophil functions.

This study evaluates a new gold-chloroquine complex [hexafluorophosphate triphenylphosphine chloroquine gold (I), Au(CQ)(PPh3)PF6, referred to hereinafter as CQAu] in terms of its anti-inflammatory and toxic effects on immune cells compared to auranofin (AF). CQAu and AF were compared for their effects on a) tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release by human lymphocytes and murine macrophages, b) functionality and survival of polymorphonuclear leukocytes (PMN), c) PMN function in the presence of human serum albumin as a competitive inhibitor, d) mitogen-induced proliferation of human lymphocytes and e) TNF-alpha and IL-6 response of mice to lipopolysaccharide (LPS). CQAu was found to be generally similar to AF, or somewhat less effective, in terms of its activity in different assays of human immune cell function. For several of the assays, this was related to the greater cytotoxicity of AF. However, the two drugs did show comparable inhibitory effects on TNF-alpha and IL-6 production in a mouse model in vitro and in vivo, which were independent of a cytotoxic effect. CQAu merits further investigation as a gold drug with potential applications in treating inflammatory disease.