10.1021/np500897y.s001
José Rivera-Chávez
José
Rivera-Chávez
Mario Figueroa
Mario
Figueroa
María del Carmen González
María
del Carmen González
Anthony E. Glenn
Anthony E.
Glenn
Rachel Mata
Rachel
Mata
α‑Glucosidase
Inhibitors from a <i>Xylaria feejeensis</i> Associated with <i>Hintonia latiflora</i>
American Chemical Society
2015
ECD spectroscopy
theory calculations
Compounds 2
IC 50 values
stereogenic centers
Molecular docking
stereochemical assignments
endophytic fungus
Hintonia latiflora
compounds bind
Xylaria feejeensis
α GHY
IC 50
Hintonia latifloraTwo
allosteric type
Xylaria feejeensis Associated
2015-04-24 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/_Glucosidase_Inhibitors_from_a_i_Xylaria_feejeensis_i_Associated_with_i_Hintonia_latiflora_i_/2173501
Two new compounds, pestalotin 4′-<i>O</i>-methyl-β-mannopyranoside
(<b>1</b>) and 3<i>S</i>,4<i>R</i>-(+)-4-hydroxymellein
(<b>2</b>), were isolated from an organic extract of a <i>Xylaria feejeensis</i>, which was isolated as an endophytic
fungus from <i>Hintonia latiflora.</i> In addition, the
known compounds 3<i>S</i>,4<i>S</i>-(+)-4-hydroxymellein
(<b>3</b>), 3<i>S</i>-(+)-8-methoxymellein (<b>4</b>), and the quinone derivatives 2-hydroxy-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione
(<b>5</b>), 4<i>S</i>,5<i>S</i>,6<i>S</i>-4-hydroxy-3-methoxy-5-methyl-5,6-epoxycyclohex-2-en-1-one
(<b>6</b>), and 4<i>R</i>,5<i>R</i>-dihydroxy-3-methoxy-5-methylcyclohexen-2-en-1-one
(<b>7</b>) were obtained. The structures of <b>1</b> and <b>2</b> were elucidated using a set of spectroscopic and spectrometric
techniques. The absolute configuration of the stereogenic centers
of <b>1</b> and <b>2</b> was determined using ECD spectroscopy
combined with time-dependent density functional theory calculations.
In the case of <b>1</b>, comparison of the experimental and
theoretical <sup>3</sup><i>J</i><sub>6–7</sub> coupling
constants provided further evidence for the stereochemical assignments.
Compounds <b>2</b> and <b>3</b> inhibited <i>Saccharomyces
cerevisiae </i>α-glucosidase (αGHY), with IC<sub>50</sub> values of 441 ± 23 and 549 ± 2.5 μM, respectively.
Their activity was comparable to that of acarbose (IC<sub>50</sub> = 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.