title: Synthesis, structural characterization and effect on human granulocyte intracellular cAMP levels of abscisic acid analogs.
abstract: The phytohormone abscisic acid (ABA), in addition to regulating physiological functions in plants, is also produced and released by several mammalian cell types, including human granulocytes, where it stimulates innate immune functions via an increase of the intracellular cAMP concentration ([cAMP]i). We synthesized several ABA analogs and evaluated the structure-activity relationship, by the systematical modification of selected regions of these analogs. The resulting molecules were tested for their ability to inhibit the ABA-induced increase of [cAMP]i in human granulocytes. The analogs with modified configurations at C-2' and C-3' abrogated the ABA-induced increase of the [cAMP]i and also inhibited several pro-inflammatory effects induced by exogenous ABA on granulocytes and monocytes. Accordingly, these analogs could be suitable as novel putative anti-inflammatory compounds.
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 5, 16132 Genoa, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bellotti
authors.affiliation: Center of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 5, 16132 Genoa, Italy; Department of Hearth Environmental and Life Science (DISTAV), University of Genoa, Corso Europa 26, 16132 Genoa, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Salis
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Grozio
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 5, 16132 Genoa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Damonte
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vigliarolo
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 16146 Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Galatini
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 5, 16132 Genoa, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Zocchi
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 5, 16132 Genoa, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Benatti
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy; Center of Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto XV 5, 16132 Genoa, Italy. Electronic address: enrico.millo@unige.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Millo
mesh_terms: D000040:Abscisic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D000040:Abscisic Acid; D000242:Cyclic AMP
keywords: Abscisic acid; Abscisic acid analogs; Granulocytes; Inflammatory disease; cAMP