(±)-Gnetuparin A: a pair of stilbene enantiomers from Gnetum parvifolium and their xanthine oxidase inhibitory activity

Abstract

(±)-Gnetuparin A (1a/1b), a pair of stilbene enantiomers characterized by a 6/5/5 tricyclic ring system, were isolated from the stems of Gnetum parvifolium. The racemic mixture of 1a/1b was separated on a chiral high-performance liquid chromatography (HPLC) column. The absolute configurations of the enantiomers were established by comprehensive spectral analysis in combination with a quantum chemical calculation. Structurally, compounds 1a/1b feature a novel skeleton based on a stilbenoid coupled with a methylcyclopentanone, forming a rare cyclopenta[b]furan-6-one motif. A hypothetical biosynthetic pathway for 1a/1b was proposed. Biological investigations showed that 1a and 1b exhibited good xanthine oxidase inhibitory activities with IC₅₀ values of 74.9 and 56.1 µM, respectively. Moreover, an enzyme kinetic analysis revealed that compound 1b acted as a noncompetitive inhibitor of xanthine oxidase with a K_i value of 54.72 μM. This study not only revealed the structure and inhibitory activity of 1a/1b against xanthine oxidase but also provides a theoretical basis for the development of new uric-acid-lowering drugs from G. parvifolium.