Discovery of derivatives from Spartina alterniflora-sourced moiety as xanthine oxidase inhibitors to lower uric acid.

In this work, hit compounds Spartinin F1-F20 sharing the Spartina alterniflora-sourced ferulic acid backbone were synthesized and evaluated on inhibiting xanthine oxidase and lowering uric acid level. The top hit Spartinin F2 exhibited inhibition percentages at 10 μM dosage as high as 84.48 (higher than that of the positive control allopurinol) and low cyto-toxicity. Spartinin F2 inferred potential efficiency in lowering the serum UA level (from 631.6 μM to 295.0 μM), which was comparable with allopurinol (to 309.2 μM). Spartinin F2 was also beneficial for other serum indexes. The bioavailability of Spartinin F2 was 63.71% from the preliminary pharmacokinetics test and the molecular docking simulation indicated that except for retaining the hydrogen bonds with the key residues such as THR 1010 and LYS 771, the introduction of the π-sulfur interactions via the sulfonate might also be beneficial for developing more potent XO inhibitors.