Alpha-glucosidase inhibitors from Sporormiella minimoides

Sporormiella minimoides is an endophytic fungus obtained from Hintonia latiflora (Rubiaceae) leaves, a medicinal plant widely used in Mexico to treat diabetes. Bioassay- guided fractionation of the organic extract of the fungus yielded the isolation of a novel metabolite characterized as 5,7'-dihydroxy-2,4',7,9'-tetramethoxy-1'H, 4H, 6'H-spiro[naphthalen-1,2'-phenalen]-4,6'-dione (1) obtained as a racemic mixture (1a and 1b). The related known compounds preussochromone C (2) and corymbiferone (3) were also isolated. Compounds 1 – 3 and acarbose (positive control) inhibited yeast α-glucosidase (IC₅₀ values of 2.91, 66.5, 155.5 and 876.9µM, respectively). Kinetic analysis revealed that 1 – 3 behaved as mixed-type inhibitors (Ki's = 2.7, 52.0 and 163.8µM, respectively). Finally, docking studies predicted that 1a could bind to the catalytic site of the enzyme (PDB code 3A4A), whereas 1b, 2 and 3 to an allosteric site.