Discovery, Characterization, and Anti-XOD Activity of Calcium Metallophore from <i>Coix lacryma-jobi</i>

In this work, coixalkyne A (<b>1</b>), a natural polynuclear calcium complex with a novel cross-shaped molecular architecture, was isolated from <i>Coix lacryma-jobi</i> L. along with the undescribed analogue coixalkyne B (<b>2</b>). Their structures were identified by means of NMR spectroscopy, ECD calculations, and single-crystal X-ray diffraction. It is noteworthy that the calcium ligands of <b>1</b> as well as compound <b>2</b> possess rare terminal alkynes and a <i>nor</i>-carbon sesquiterpene (C14) framework. The antihyperuricemic activity of <i>C. lacryma-jobi</i> and xanthine oxidase (XOD) inhibitory effects of <b>1</b>-<b>2</b> were elucidated by <i>in vivo</i> and <i>in vitro</i> assays, while the possible mechanism of action was suggested by molecular docking. Different from the reported chemical synthesis and protein calcium carriers, the discovery of compounds <b>1</b> and <b>2</b> provided new proof for the natural calcium metallophore in plants with xanthine oxidase inhibitory activity.