Preussilides A−F, Bicyclic Polyketides from the Endophytic Fungus Preussia similiswith Antiproliferative Activity

Abstract

Six novel bioactive bicyclic polyketides (1−6) were isolated from cultures of an endophytic fungus of the medicinal plantGlobularia alypumcollected in Batna, Algeria. The producer organism was identified asPreussia similisusing morphological and molecular phylogenetic methods. The structures of metabolites1−6, for which the trivial names preussilides A−F are proposed, were elucidated using a combination of spectral methods, including extensive 2D NMR spectroscopy, high-resolution mass spectrometry, and CD spectroscopy. Preussilides were tested for antimicrobial and antiproliferative effects, and, in particular, compounds 1and3showed selective activities against eukaryotes. Subsequent studies on the influence of1and3 on the morphology of human osteosarcoma cells (U2OS) suggest that these two polyketides might target an enzyme involved in coordination of the cell division cycle. Hence, they might, for instance, affect timing or spindle assembly mechanisms, leading to defects in chromosome segregation and/or spindle geometry