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

The phytohormone abscisic acid (ABA), in addition to regulating physiological functions in plants, is alsoproduced and released by several mammalian cell types, including human granulocytes, where it stim-ulates 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 system-atical modification of selected regions of these analogs. The resulting molecules were tested for their abil-ity to inhibit the ABA-induced increase of [cAMP]i in human granulocytes. The analogs with modifiedconfigurations at C-20and C-30abrogated the ABA-induced increase of the [cAMP]i and also inhibited sev-eral pro-inflammatory effects induced by exogenous ABA on granulocytes and monocytes. Accordingly,these analogs could be suitable as novel putative anti-inflammatory compounds. © 2014 Elsevier Ltd. All rights reserved.