Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 23, Issue 1, Pages 22-32Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2014.11.035
Keywords
Abscisic acid; Abscisic acid analogs; cAMP; Granulocytes; Inflammatory disease
Funding
- Italian Ministry of Education University and Scientific Research
- University of Genova
- Fondazione CARIGE
- Compagnia di S. Paolo
- Regione Liguria
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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. (C) 2014 Elsevier Ltd. All rights reserved.
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