title: Synthesis and characterization of new copper- and zinc-chloroquine complexes and their activities on respiratory burst of polymorphonuclear leukocytes.
abstract: 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. Both effects were dose-dependent, with an IC50 of approximately 10 microM. With the same stimulants, there was only modest inhibition of ROS generation by any of the zinc-chloroquine complexes 4-5 at 10-100 microM. All complexes did not show significant in vitro toxicity as assayed by the trypan blue exclusion method. Our results reinforce previous observations that many metal derivatives of anti-inflammatory drugs affect neutrophil functions with higher potency than their parent ligands.
authors.affiliation: Centro de Química, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela. mnavarro@ivic.ve
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro
authors.forename: Helen
authors.initials: H
authors.lastname: Goitia
authors.forename: Pedro
authors.initials: P
authors.lastname: Silva
authors.forename: Mait
authors.initials: M
authors.lastname: Velásquez
authors.forename: Luis E
authors.initials: LE
authors.lastname: Ojeda
authors.forename: Germán
authors.initials: G
authors.lastname: Fraile
mesh_terms: D002738:Chloroquine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008163:Luminescent Measurements; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D017967:Zinc Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017967:Zinc Compounds; D003300:Copper; D002738:Chloroquine