Design, synthesis and molecular modeling of aloe-emodin derivatives as potent xanthine oxidase inhibitors

• We designed and synthesized a series of aloe-emodin derivatives.
• We evaluated the xanthine oxidase–inhibition activities of those compounds.
• The compound A1 possessed the best activity with IC50 of 2.79 μM.
• We identified A1 was a mixed-type xanthine oxidase inhibitor.
• Using the docking study we found A1 could interact with the catalyze site of xanthine oxidase.

A series of aloe-emodin derivatives were synthesized and evaluated as xanthine oxidase inhibitors. Among them, four aloe-emodin derivatives showed significant inhibitory activities against xanthine oxidase. The compound 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carbaldehyde (A1) possessed the best xanthine oxidase inhibitory activity with IC50 of 2.79 μM. Lineweaver–Burk plot analysis revealed that A1 acted as a mixed-type inhibitor for xanthine oxidase. The docking study revealed that the molecule A1 had strong interactions with the active site of xanthine oxidase and this result was in agreement with kinetic study. Consequently, compound A1 is a new-type candidate for further development for the treatment of gout.

The structure of compound A1 and the expected interaction between compound A1 and the binding site of XDH (PDB NO. 1VDV).Figure optionsDownload as PowerPoint slide