title: 3-Phenylcoumarin derivatives selectively modulate different steps of reactive oxygen species production by immune complex-stimulated human neutrophils.
abstract: Immune complex (IC) deposition in tissues triggers the release of harmful oxidant and lytic compounds by neutrophils. We examined how ten 3-phenylcoumarin derivatives affect the reactive oxygen species (ROS) production by IC-stimulated human neutrophils. Most of the 3-phenylcoumarins inhibited the luminol-enhanced chemiluminescence (CL-lum) more strongly than they inhibited the lucigenin-enhanced chemiluminescence (CL-luc), without clear signs of toxicity. The most effective CL-lum inhibitors, 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin (5) and 6,7-dihydroxy-3-[3',4'-dihydroxyphenyl]-coumarin (19), also inhibited myeloperoxidase activity more potently and had higher hypochlorous acid scavenging ability, but did not affect the NADPH-oxidase activity. The type, number, and position of the substituent influenced the pharmacological effects of 3-phenylcoumarins; however, the structural requirements for CL-lum and CL-luc inhibition were a little different. Compounds 5 and 19 are promising prototypes of therapeutic molecules to modulate ROS production by neutrophils in IC-mediated inflammatory diseases.
authors: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Avenida Bandeirantes n. 3900, CEP 14049-900, Ribeirão Preto, SP, Brazil.
authors: Micássio F
authors: MF
authors: Andrade
authors: Luciana M
authors: LM
authors: Kabeya
authors: Ana Elisa C S
authors: AE
authors: Azzolini
authors: Everton O L
authors: EO
authors: Santos
authors: Andréa S G
authors: AS
authors: Figueiredo-Rinhel
authors: Márcio R P
authors: MR
authors: Paris
authors: Flávio S
authors: FS
authors: Emery
authors: Mônica T
authors: MT
authors: Pupo
authors: Yara M
authors: YM
authors: Lucisano-Valim
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology; D002478:Cells, Cultured; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology; D056747:Immunomodulation; D008163:Luminescent Measurements; D058990:Molecular Targeted Therapy; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010084:Oxidation-Reduction / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000936:Antigen-Antibody Complex; D003374:Coumarins; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C030123:coumarin; D009195:Peroxidase