Sulfur-containing benzofurans and a-pyrones from the mangrove-derived fungus Talaromyces sp. WHUF0341

Two new sulfur-containing benzofurans, talarobenzofurans A and B (1 and 2), one new benzofuran talarobenzofuran C (3) and two new alpha-pyrones talaropyrones A and B (5 and 6), along with five known compounds eurothiocin A (4), nodulisporipyrone A (7), peniazaphilin B (8), ramulosin (9) and 6-hydroxyramulosin (10) were isolated and identified from the culture extract of the mangrove-derived fungus Talaromyces sp. WHUF0341 guided by OSMAC (one strain-many compounds) strategy. Their structures were established by extensive spectroscopic data analysis, the modified Mosher's method and electronic circular dichroism (ECD) calculations. Structurally, compounds 1 and 2 possesed the unique thioester moiety derived from benzofuran and 2-hydroxy-3-mercaptopropionic acid, which was rarely-observed in natural products. The alpha-glucosidase inhibitory and antibacterial activities of the isolated compounds were evaluated. Compounds 3 and 4 exhibited inhibitory effects against alpha-glucosidase activity with IC50 values of 48.9 & PLUSMN; 2.16 and 8.8 & PLUSMN; 1.08 mu M, respectively. The inhibitory type of 3 on alpha-glucosidase was determined as non-competitive-type inhibition with K (i) value of 242.3 mu M by using Lineweaver-Burk double reciprocal and Dixon single reciprocal plots. Meanwhile, the binding model of 3 and 4 with alpha-glucosidase was determined by molecular docking assay. The biosynthetic pathways of compounds 1-4 were also proposed. This study suggested that benzofurans 3 and 4 could be potential lead compounds for the hypoglycemic drugs.