α-Glucosidase Inhibitors from a Xylaria feejeensis Associated with Hintonia latiflora

Two new compounds, pestalotin 4'-O-methyl-beta-mannopyranoside (1) and 3S,4R-(+)-4-hydroxymellein (2), were isolated from an organic extract of a Xylaria feejeensis, which was isolated as an endophytic fungus from Hintonia latiflora. In addition, the known compounds 3S,4S-(+)-4-hydroxymellein (3), 3S-(+)-8-methoxymellein (4), and the quinone derivatives 2-hydroxy-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione (5), 4S,5S,6S-4-hydroxy-3-methoxy-5-methyl-5,6-epoxycyclohex-2-en-1-one (6), and 4R,5R-dihydroxy-3-methoxy-5-methylcyclohexen-2-en-1-one (7) were obtained. The structures of 1 and 2 were elucidated using a set of spectroscopic and spectrometric techniques. The absolute configuration of the stereogenic centers of 1 and 2 was determined using ECD spectroscopy combined with time-dependent density functional theory calculations. In the case of 1, comparison of the experimental and theoretical (3)J(6-7) coupling constants provided further evidence for the stereochemical assignments. Compounds 2 and 3 inhibited Saccharomyces cerevisiae a-glucosidase (alpha GHY), with IC50 values of 441 +/- 23 and 549 +/- 2.5 mu M, respectively. Their activity was comparable to that of acarbose (IC50 = 545 +/- 19 mu M), used as positive control. Molecular docking predicted that both compounds bind to alpha GHY in a site different from the catalytic domain, which could imply an allosteric type of inhibition.