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.

Synthesis and characterization of new copper- and zinc-chloroquine complexes and their activities on respiratory burst of polymorphonuclear leukocytes.

The metal-chloroquine (CQ) complexes, Cu(CQ)2Cl (1), Cu(CQ)(PPh3)(NO3) (2), [Cu(OAc)2(CQ)]2 (3) ZnCl2(CQ)(H2O)2 (4), [Zn(OAc)2(CQ)(H2O)]2 (5), were synthesized and characterized by NMR, FAB-mass, elemental analysis, and UV-Vis, EPR and IR spectroscopies. The effects of these compounds on the generation of reactive oxygen species (ROS) from human neutrophils (PMNs) were tested in the concentration range 1-100 microM and compared to that of chloroquine. The data show that the copper-chloroquine complexes 1-3 inhibit neutrophil release of ROS in PMNs activated either by a phorbol ester or by phagocytosable particles.

In vitro activities of transition metal derivatives of ketoconazole and clotrimazole against a wild type strain of Saccharomyces cerevisiae in absence or presence of human neutrophils.

In vitro activities of a series of gold, copper and ruthenium clotrimazole (CTZ, CAS 23593-75-1) and ketoconazole (KTZ, CAS 65277-42-1) derivatives were investigated individually and in combination with human neutrophils (PMNs) against a wild type strain of Saccharomyces cerevisiae. For 11 out of 12 tested metal complexes, the minimal inhibitory concentrations (MICs) at which 100 % of yeast growth was inhibited ranged from 0.75 to 3.

Effects of gold-chloroquine complexes on respiratory burst of polymorphonuclear leukocytes.

The effects of gold-chloroquine derivatives with the formula [Au(PR3)(CQ)]PF6 (where R = Ph (1), Et or Me) on the superoxide anion production by human neutrophils (PMNs, polymorphonuclear cells) were investigated. When these complexes (0.1-3 mumol/l) were added to PMNs prior to the activators formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), they inhibited isoluminol-horseradish peroxidase-dependent chemiluminescence (CLisol).