title: Alkaloids from the Fungus Penicillium spathulatum as α-Glucosidase Inhibitors.
abstract: Benzomalvin A (1), quinolactacins A1 (2), A2 (3) and B (4), quinolonimide (5), asperphenamate (6), and a new halogenated polyhydroxyanthraquinone, namely 2-chloro-6-[2'(S)-hydroxypropyl]-1,3,8-trihydroxy-anthraquinone (7), were isolated from an organic extract obtained from the solid culture of Penicillium spathulatum B35. Compounds 2 and 3 were isolated as an epimeric mixture, and compound 4 as a racemate. The structure of 7 was elucidated using 1D and 2D NMR, combined with computational methods (density functional theory). Compound 1, the mixture of 2 and 3, racemate 4, and compound 6 inhibited the yeast α-glucosidase in a concentration-dependent fashion with IC50 values of 383.2, 273.3, 57.3, and 8.3 µM, respectively. The α-glucosidase inhibitory properties of 1 were confirmed in vivo with an oral sucrose tolerance test in normal and hyperglycemic mice (p < 0.05). Furthermore, docking studies predicted that the most stable conformers of 1 bind to yeast and mammalian α-glucosidases with a higher affinity than acarbose. Finally, 1 also showed antihyperalgesic activity when tested in the formalin assay in hyperglycemic mice (p < 0.05).
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: Paulina
authors.initials: P
authors.lastname: Del Valle
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: Ana-Laura
authors.initials: AL
authors.lastname: Martínez
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: Mario
authors.initials: M
authors.lastname: Figueroa
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, USA.
authors.forename: Huzefa A
authors.initials: HA
authors.lastname: Raja
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: Rachel
authors.initials: R
authors.lastname: Mata
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D015394:Molecular Structure; D010407:Penicillium / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D065089:Glycoside Hydrolase Inhibitors; D000520:alpha-Glucosidases