Discovery of coumaric acid derivatives hinted by coastal marine source to seek for uric acid lowering agents

• Published in: Journal of enzyme inhibition and medicinal chemistry 2023-12, Vol.38 (1), p.2163241-2163241
• Main Authors: Yang, Yu-Shun, Wang, Bin, Liu, Junzhong, Li, Qin, Jiao, Qin-Cai, Qin, Pei
• Format: Article
• Language: English
• Subjects: Allopurinol; Allopurinol - pharmacology; Allopurinol - therapeutic use; Animal models; Animals; Antioxidants; Biotechnology; Chromatography; Coastal marine sources; Coumaric acid; Coumaric Acids; Cytotoxicity; Humans; Hyperuricemia - drug therapy; Libraries; Life sciences; lowering uric acid; Mice; Nonnative species; Pharmaceuticals; Pharmacokinetics; Public health; Research Paper; Software; Spartina alterniflora; Uric acid; Uric Acid - therapeutic use; Xanthine oxidase; Xanthine Oxidase - metabolism; xanthine oxidase inhibition
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2022.2163241

In this work, a series of novel compounds Spartinin C1-C24 were screened, synthesised and evaluated for inhibiting xanthine oxidase thus lowering serum uric acid level. The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 μM dosage, which were higher than the positive control Allopurinol. They were low cytotoxic onto human normal hepatocyte cells. Treatment with Spartinin C10 could lower the serum uric acid level to 440.0 μM in the hyperuricemic model mice (723.0 μM), comparable with Allopurinol (325.8 μM). Spartinin C10 was more appreciated than Allopurinol on other serum indexes. The preliminary pharmacokinetics evaluation indicated that the rapid absorption, metabolism and elimination of Spartinin C10 should be further improved. The discovery of pharmaceutical molecules from coastal marine source here might inspire the inter-disciplinary investigations on public health.