Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia mangostana

Abstract

This study was designed to gain deeper insights into the molecular properties of natural xanthones as neuraminidase inhibitors. A series of xanthones 1– 12 was isolated from the seedcases of Garcinia mangostana and evaluated for bacteria neuraminidase inhibitory activity. Compounds 11 and 12 emerged to be new xanthones (mangostenone F, mangostenone G) which we fully spectroscopically characterized. The IC 50 values of compounds 1– 12 were determined to range between 0.27–65.7 μM. The most potent neuraminidase inhibitor 10 which has an IC 50 of 270 nM features a 5,8-diol moiety on the B ring. Interestingly, structure–activity studies reveal that these xanthones show different kinetic inhibition mechanisms depending upon the arrangement of hydroxyl groups in the B ring. Compound 6 possessing a 6,7-diol motif on the B-ring operated under the enzyme isomerization model ( k 5 = 0.1144 μM −1 s −1, k 6 = 0.001105 s −1, and K i app = 7.41 μM), whereas compound 10 possessing a 5,8-diol unit displayed simple reversible slow-binding inhibition ( k 3 = 0.02294 μM −1 s −1, k 4 = 0.001025 s −1, and K i app = 0.04468 μM).