Chloro-containing polyketides with anti-neuroinflammatory and anti-angiogenic activities from a coralline algicolous fungal strain Diaporthe middletonii Km3279.

In this study, a fungal strain Diaporthe middletonii Km3279, was isolated from the coralline alga Corallina declinata collected in Lieyu Township, Kinmen County, Taiwan, and subsequently identified. Liquid fermentation was carried out using the OSMAC (one strain, many compounds) strategy, with cultures grown in freshwater potato dextrose broth, brackish water (17 ‰) with malt extract (ME) medium, and freshwater ME medium supplemented with 0.03 % potassium iodide for 14-21 days. Following fermentation, all culture broths were extracted with ethyl acetate. The resulting dried extracts were then sequentially separated and purified by Sephadex LH-20 open-column chromatography, medium-pressure liquid chromatography, and high-performance liquid chromatography. This process led to the isolation and characterization of seven previously undescribed polyketides, designated diaportonicins A-G (1-7), along with five known compounds: periconsin D (8), cryptosporiopsinol (9), periconsin B (10), periconsin E (11), and (S)-6-hydroxymellein (12). In anti-neuroinflammatory assays, compounds 5, 8, 11, and 12 showed potent inhibitory effects on nitric oxide production in murine microglial BV-2 cells with IC50 values of 1.39 ± 0.26, 0.58 ± 0.07, 9.86 ± 1.91, and 6.19 ± 1.30 μM, respectively, and without detectable cytotoxicity. In addition, compounds 5, 7, and 9 exhibited moderate to strong anti-angiogenic activities by inhibiting tube formation in endothelial progenitor cells, with IC50 values of 8.00 ± 1.00, 5.00 ± 1.00, and 26.00 ± 2.00 μM, respectively. A putative biosynthetic pathway for compounds 1-11 is also proposed.