Glucoconjugated monoterpene indole alkaloids with xanthine oxidase inhibitory activity from Ophiorrhiza japonica.

Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1–5), ophiorglucidines A-E, and seven known analogues (6–12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3 , both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC 50 = 11.1 μ M) with IC 50 values of 1.0 μ M, and 2.5 μ M, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids. [Display omitted] • Five undescribed alkaloids are identified from Ophiorrhiza japonica. • For the first time, the inner salt indole alkaloid glycosides were found to have an inhibitory effect on xanthine oxidase. • The key pharmacophore with inhibitory activity was identified. [ABSTRACT FROM AUTHOR]