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

Rivera-Chávez, José, Figueroa, Mario, González, María del Carmen, Glenn, Anthony E., Mata, Rachel
Journal of natural products 2015 v.78 no.4 pp. 730-735
Saccharomyces cerevisiae, Xylaria, acarbose, active sites, alpha-glucosidase, endophytes, fungi, inhibitory concentration 50, molecular models, spectroscopy
Two new compounds, pestalotin 4′-O-methyl-β-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 ³J₆–₇ coupling constants provided further evidence for the stereochemical assignments. Compounds 2 and 3 inhibited Saccharomyces cerevisiae α-glucosidase (αGHY), with IC₅₀ values of 441 ± 23 and 549 ± 2.5 μM, respectively. Their activity was comparable to that of acarbose (IC₅₀ = 545 ± 19 μM), used as positive control. Molecular docking predicted that both compounds bind to αGHY in a site different from the catalytic domain, which could imply an allosteric type of inhibition.