(S)-(+)-Decursin and its Analogues as Inhibitors of Cytokines Secretion Induced by DpE in THP-1/EoL-1 Cell Line

(S)-(+)-Decursin and its analogues were synthesized and evaluated for their inhibitory effects on monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and IL-6 secretion induced by Dermatophagoides pteronyssinus extract (DpE) in human acute monocytic leukemia (THP-1) cells and eosinophilic leukemia (EoL-1) cell lines. (S)-(+)- Decursin analogues with alkyl acryloyl groups, apart from (S)-(+)-decursin (1) and (S)-(+)-decursinol angelate (4a), did not influence the regulation of cytokine secretion. (S)-(+)-Decursin analogues (8d, 8f, 8g) with cinnamoyl groups carrying hydroxyl- and acetoxy-substitutes potently inhibited the secretion of MCP-1 and IL-6. The structure-activity relationship study revealed that increasing π-rich environment at the extensions from the eastern alcohol of (S)-(+)-decursin is a key element in building the pharmacophore for achieving the desired biological activity.