Effect of a gold-chloroquine complex on inflammation-related leukocyte functions and cell viability. Comparison with auranofin.
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.
Navarro
Maribel
M
Centro de Química, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
Fraile
Germán
G
Velásquez
Mait
M
González
Eglys
E
Escalona
Jessnell
J
Ilanjian
Rita
R
Abad
María Jesús
MJ
Taylor
Peter
P
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology*; D005260:Female; D006046:Gold / Q000494:pharmacology*; D007202:Indicators and Reagents; D007249:Inflammation / Q000473:pathology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018501:Antirheumatic Agents; D007202:Indicators and Reagents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D001310:Auranofin; D006046:Gold; D002738:Chloroquine