title: N-Aryl-2-phenyl-2,3-dihydro-imidazo[1,2-b]pyrazole-1-carboxamides 7-substituted strongly inhibiting both fMLP-OMe- and IL-8-induced human neutrophil chemotaxis.
abstract: Anomalous activation of neutrophil recruitment is one of the causes of many inflammatory diseases. The chemoattractants N-formyl-methionyl-leucyl-phenylalanine (fMLP), and interleukine 8 (IL8) play a pivotal role in neutrophil chemotaxis regulation in the latter and early stages, respectively, probably by two independent mechanisms. We reported here synthesis and biological evaluation of new N-aryl-2-phenyl-2,3-dihydro-imidazo[1,2-b]pyrazole-1-carboxamides 7-substituted which were designed as possible multi-target antiinflammatory agents. Many of the title compounds showed a good inhibition, in the nano molar range, of human neutrophil chemotaxis selectively acting toward fMLP-OMe (methylester of fMLP) or IL8 stimulus; whereas, two compounds showed an interesting dual activity inhibiting both fMLP-OMe and IL8-induced chemotaxis at nano molar concentration.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, viale Benedetto XV, 3, 16132 Genova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Brullo
authors.forename: Susanna
authors.initials: S
authors.lastname: Spisani
authors.forename: Rita
authors.initials: R
authors.lastname: Selvatici
authors.forename: Olga
authors.initials: O
authors.lastname: Bruno
mesh_terms: D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D016209:Interleukin-8 / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016209:Interleukin-8; D011720:Pyrazoles; C031280:pyrazole; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester