Antagonism of human formyl peptide receptor 1 with natural compounds and their synthetic derivatives

- We review natural products reported to antagonize or inhibit FPR1-mediated responses.
- Results of additional screening of natural compounds for their ability to antagonize FPR1 are presented and discussed.
- We also use molecular modeling to predict how well natural compounds fit the FPR1 antagonist pharmacophore.
- Characterization of natural products that antagonize FPR1 may have potential for the development of novel therapeutics.

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 Ca2 + 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.