Unprecedented Antimicrobial and Cytotoxic Polyketides from Cultures of Diaporthe africana sp. nov.

Abstract

Four unprecedented polyketides named isoprenylisobenzofuran B (2), isoprenylisobenzofuran C1/C2 (3), diaporisoindole F1/F2 (4), and isochromophilonol A1/A2 (7) were isolated from ethyl acetate extracts of the newly described endophytic fungus Diaporthe africana. Additionally, the previously reported cyclic depsipeptide eucalactam B (1) was also identified, along with the known compounds diaporisoindole A/B (5), tenellone B (6) and beauvericin (8). The taxonomic identification of the fungus was accomplished using a polyphasic approach combining multi-gene phylogenetic analysis and microscopic morphological characters. The structures 1–8 were determined by a detailed analysis of their spectral data, namely high-resolution electrospray ionization mass spectrometry (HR-ESIMS), 1D/2D nuclear magnetic resonance (NMR) spectroscopy, as well as electronic circular dichroism (ECD) spectra. In addition, chemical methods such as Marfey’s analysis were also employed to determine the stereochemistry in compound 1. All the compounds obtained were evaluated for antimicrobial and in vitro cytotoxic properties. Compounds 3–8 were active against certain fungi and Gram-positive bacteria with MIC values of 8.3 to 66.6 µg/mL. In addition, 3–5 displayed cytotoxic effects (22.0 ≤ IC50 ≤ 59.2 µM) against KB3.1 and L929 cell lines, whereas compounds 6–8 inhibited the growth of seven mammalian cancer cell lines with IC50 ranging from 17.7 to 49.5 µM (6), 0.9 to 12.9 µM (7) and 1.9 to 4.3 µM (8).