Identification of novel chromenone derivatives as interleukin-5 inhibitors

A series of (E)-5-alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones (4) and (E)-5-alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones (5) were synthesized and evaluated for their IL-5 inhibitory activity. Propenone analogs 4 possess some of the structurally important characteristics of isoflavone 2 and chalcone 3 previously known as potent IL-5 inhibitor. However, the inhibitory activity of 4 was weak and therefore this structural hybridization appears to be ineffective for the design of IL-5 inhibitor. Meanwhile the potent activity profile of compounds 5 was discovered. This enhanced activity of 5 compared to 4 could be due to the effective location of hydroxyl group of allylic alcohol moiety of 5 in the 3D structure. The electron withdrawing substituents at position 4 of phenyl ring of 5 enhances the activity possibly due to an increase in the strength of hydrogen bonding property of hydroxyl group of allylic alcohol moiety.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel chromenones were prepared and tested for their IL-5 inhibitory activity. ► (E)-5-Alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones are weak inhibitor. ► (E)-5-Alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones are potent.