The secondary metabolites of the alga-derived fungus Aspergillus niveoglaucus КММ 4176 and their antimicrobial and antibiofilm activities.

Marine alga-derived fungal strain КММ 4176 was identified as Aspergillus niveoglaucus based on ITS region BenA, CaM and RPB2 gene sequence analysis. The anthraquinone derivatives emodin anthrone (1) and 4-hydroxyemodin anthrone (2), chromone derivative aloesone (3), and indole diketopiperazine alkaloid neoechinulin B (4) were isolated from the ethyl acetate extract of this fungus. In addition, UPLC MS data analysis of the KMM 4176 extract showed the presence of 17 echinulin-family alkaloids, as well as their biogenetic precursor cyclo(L-alanyl-L-tryptophyl) and a number of polyketide compounds. Emodin anthrone and 4-hydroxyemodin anthrone were found as inhibitors of biofilm formation by Staphylococcus aureus with half-maximal inhibitory concentrations (IC₅₀) of 5.5 µM and 23.7 µM, respectively. Moreover, emodin anthrone (1) and 4-hydroxyemodin anthrone (2) inhibited staphylococcal sortase A activity with IC₅₀ of 9.2 µM and 37.6 µM, respectively. Aloesone (3) also inhibited S. aureus biofilm formation but was less active. The first data on neoechinulin B (4) antibiofilm activity and sortase A inhibition were obtained. The positive effects of the isolated compounds on the growth of HaCaT keratinocytes infected with S. aureus were also observed.