Novel synthetic strategy for aromatic ether coumarin derivatives and evaluation of anti-allergic potential.

OBJECTIVES

The study aimed to explore novel aromatic ether coumarins as potential anti-allergic lead compounds.

METHODS

The benzene ring of hypervalent iodine compounds was strategically introduced into the coumarin framework to facilitate the efficient synthesis of aromatic ether coumarin derivatives via the one-pot method. Two representative compounds, namely, 4-phenylether coumarin and 7-phenylether coumarin, were successfully designed and synthesized. The compounds were structurally characterized using spectroscopic techniques, including nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared (IR) spectroscopy. Their inhibitory effects on both IgE- and non-IgE-mediated degranulation of rat basophilic leukemia (RBL-2H3) cells and mouse bone marrow derived mast cells (BMMCs) were subsequently evaluated.

RESULTS

Three representative 7-phenylether coumarins (4, 5, and 6) and 4-phenylether coumarin (7) were synthesized with high efficiency. The compounds exhibited potent anti-allergic effects, indicated by the marked inhibition of degranulation and β-HEX release from RBL-2H3 cells and BMMCs. The inhibitory effects of 7-phenylether 3-methyl ketocoumarin (6) were found to be superior to those of the tested compounds.

CONCLUSION

Aromatic ether coumarins can be efficiently constructed via the oxidation of hydroxycoumarins with hypervalent iodine compounds. Compound 6 inhibited both IgE-induced and calcium ionophore (A23187)-mediated degranulation of BMMCs, warranting further in-depth investigation into its pharmacogenetic and therapeutic potential.