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

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

  • Bioorg Med Chem Lett. 2022 Oct 1:73:128907. doi: 10.1016/j.bmcl.2022.128907.
Yu-Shun Yang 1,  Bin Wang 2,  Kang-Min Zhou 2,  Junzhong Liu 2,  Qin-Cai Jiao 3,  Pei Qin 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China; Research and Development Center, Nanjing Shibeitai Biotechnology Co., Ltd., Nanjing 210003, China. Electronic address: [email protected].
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China. Electronic address: [email protected].
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China; Research and Development Center, Nanjing Shibeitai Biotechnology Co., Ltd., Nanjing 210003, China. Electronic address: [email protected].
PMID: 35902063 DOI: 10.1016/j.bmcl.2022.128907
Abstract

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.

Keywords

Lowering uric acid; Potential agent; Spartina alterniflora; Xanthine oxidase inhibition.

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