title: Antagonism of human formyl peptide receptor 1 with natural compounds and their synthetic derivatives.
abstract: Formyl peptide receptor 1 (FPR1) regulates a wide variety of neutrophil functional responses and plays an important role in inflammation and the pathogenesis of various diseases. To date, a variety of natural and synthetic molecules have been identified as FPR1 ligands. Here, we review current knowledge on natural products and natural product-inspired small molecules reported to antagonize and/or inhibit the FPR1-mediated responses. Based on this literature, additional screening of selected commercially available natural compounds for their ability to inhibit fMLF-induced Ca(2+) mobilization in human neutrophils and FPR1 transfected HL-60 cells, and pharmacophore modeling, natural products with potential as FPR1 antagonists are considered and discussed in this review. The identification and characterization of natural products that antagonize FPR1 activity may have potential for the development of novel therapeutics to limit or alter the outcome of inflammatory processes.
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, United States.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Schepetkin
authors.affiliation: Department of Biotechnology and Organic Chemistry, Tomsk Polytechnic University, Tomsk 634050, Russia; Department of Chemistry, Altai State Technical University, Barnaul, Russia.
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Khlebnikov
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, United States.
authors.forename: Liliya N
authors.initials: LN
authors.lastname: Kirpotina
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, United States. Electronic address: mquinn@montana.edu.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Quinn
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D008024:Ligands; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy / Q000379:methods; D009504:Neutrophils / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D001688:Biological Products; C469986:FPR1 protein, human; D008024:Ligands; D010455:Peptides; D044042:Receptors, Formyl Peptide
keywords: Ca(2+) flux; Formyl peptide receptor 1; Molecular modeling; Natural compound; Neutrophil; Neutrophil elastase; Receptor antagonist; Superoxide anion radical