Antibacterial Isoquinoline Alkaloids from the Fungus Em19.

In the search for new microbial antibacterial secondary metabolites, two new compounds ( and ) were isolated from culture broths of Em19. Structure determination by nuclear magnetic resonance and mass spectrometry identified the compounds as 6,7-dihydroxy-5,10-dihydropyrrolo[1,2-]isoquinoline-3-carboxylic acid (, spathullin A) and 5,10-dihydropyrrolo[1,2-]isoquinoline-6,7-diol (, spathullin B). The two compounds displayed activity against both Gram-negative and -positive bacteria, including , , , , , and . Compound was more potent than against all tested pathogens, with minimal inhibitory concentrations down to 1 µg/mL (5 µM) against , but was also more cytotoxic than (50% inhibitory concentrations 112 and 11 µM for compounds and , respectively, towards Huh7 cells). Based on stable isotope labelling experiments and a literature comparison, the biosynthesis of was suggested to proceed from cysteine, tyrosine and methionine via a non-ribosomal peptides synthase like enzyme complex, whereas compound was formed spontaneously from by decarboxylation. Compound was also easily oxidized to the 1,2-benzoquinone . Due to the instability of compound and the toxicity of , the compounds are of low interest as possible future antibacterial drugs.