title: α-Glucosidase Inhibitors from a Xylaria feejeensis Associated with Hintonia latiflora.
abstract: 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 (3)J6-7 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.
authors.affiliation: †Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Rivera-Chávez
authors.affiliation: †Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Figueroa
authors.affiliation: §Instituto de Biología, Universidad Nacional Autónoma de México, México DF 04510, Mexico.
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: González
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Glenn
authors.affiliation: †Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, Mexico.
authors.forename: Rachel
authors.initials: R
authors.lastname: Mata
mesh_terms: D020909:Acarbose / Q000494:pharmacology; D000465:Algorithms; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D049934:Isocoumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008358:Mannose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008800:Mexico; D015394:Molecular Structure; D019666:Rubiaceae / Q000382:microbiology*; D013098:Xylariales / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000187:drug effects*
chemical_list: C000600633:4-hydroxymellein; D065089:Glycoside Hydrolase Inhibitors; D049934:Isocoumarins; C000600632:pestalotin 4'-O-methyl-beta-mannopyranoside; D000520:alpha-Glucosidases; D008358:Mannose; D020909:Acarbose