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

Four unprecedented polyketides named isoprenylisobenzofuran B ( 2 ), isoprenylisobenzofuran C 1 /C 2 ( 3 ), diaporisoindole F 1 /F 2 ( 4 ), and isochromophilonol A 1 /A 2 ( 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 ≤ IC 50 ≤ 59.2 µM) against KB3.1 and L929 cell lines, whereas compounds 6 - 8 inhibited the growth of seven mammalian cancer cell lines with IC 50 ranging from 17.7 to 49.5 µM ( 6 ), 0.9 to 12.9 µM ( 7 ) and 1.9 to 4.3 µM ( 8 ).