Synthesis, structural characterization and effect on human granulocyte intracellular cAMP levels of abscisic acid analogs

Marta Bellotti; Annalisa Salis; Alessia Grozio; Gianluca Damonte; Tiziana Vigliarolo; Andrea Galatini; Elena Zocchi; Umberto Benatti; Enrico Millo

doi:10.1016/j.bmc.2014.11.035

Synthesis, structural characterization and effect on human granulocyte intracellular cAMP levels of abscisic acid analogs

Bioorg Med Chem. 2015 Jan 1;23(1):22-32. doi: 10.1016/j.bmc.2014.11.035. Epub 2014 Nov 27.

Authors

Marta Bellotti¹, Annalisa Salis², Alessia Grozio³, Gianluca Damonte¹, Tiziana Vigliarolo³, Andrea Galatini⁴, Elena Zocchi¹, Umberto Benatti¹, Enrico Millo⁵

Affiliations

¹ 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.
² 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.
³ Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy.
⁴ Department of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 16146 Genoa, Italy.
⁵ 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.

PMID: 25496807
DOI: 10.1016/j.bmc.2014.11.035

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.

Keywords: Abscisic acid; Abscisic acid analogs; Granulocytes; Inflammatory disease; cAMP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abscisic Acid / analogs & derivatives*
Abscisic Acid / chemical synthesis
Abscisic Acid / chemistry
Abscisic Acid / pharmacology*
Cyclic AMP / metabolism*
Granulocytes / drug effects*
Granulocytes / metabolism*
Humans
Intracellular Membranes / drug effects
Signal Transduction
Structure-Activity Relationship

Substances

Abscisic Acid
Cyclic AMP