Antimicrobial, antiproliferative, cytotoxic, and tau inhibitory activity of rubellins and caeruleoramularin produced by the phytopathogenic fungus Ramularia collo-cygni.

Photodynamically active anthraquinone derivatives produced by the phytopathogenic fungus Ramularia collo-cygni are known to cause a barley leaf-spot disease, but data about light-dependent and independent bioactivity have been sparse to date. We therefore conducted for the first time a broad bioactivity profiling of rubellins B, C, D, and E and caeruleoramularin. Antibacterial but not antiviral activity is reported with light-dependent increase. Furthermore, when tested without illumination, compounds exerted antiproliferative and cytotoxic activity in a series of human tumor cell lines. Inhibition of tau protein assembly was observed as well.

Uredinorubellins and caeruleoramularin, photodynamically active anthraquinone derivatives produced by two species of the genus ramularia.

Both the phytopathogenic fungus Ramularia collo-cygni and the hyperparasite R. uredinicola biosynthesize a number of red and yellow anthraquinone derivatives called rubellins. The new compounds uredinorubellins I and II, which were isolated from R. uredinicola, contribute to understanding the biosynthesis pathway that leads from simple anthraquinones to the rubellins. In addition, we isolated for the first time such simple compounds as chrysophanol and helminthsporin from both Ramularia species. A blue compound isolated from the mycelium of R. collo-cygni was revealed to be a unique 9,4-anthracenedione derivative. Structure elucidation by (1)H and (13)C NMR of the new but unstable compound caeruleoramularin was possible only by feeding the fungus different labeled (13)C acetates. The photodynamic activity of the uredinorubellins was comparable to rubellin D, whereas chrysophanol and caeruleoramularin did not display such activity.

Biosynthesis of photodynamically active rubellins and structure elucidation of new anthraquinone derivatives produced by Ramularia collo-cygni.

Here we present the first isolation of the anthrachinone derivative rubellin A out of mycelium and culture filtrate of Ramularia collo-cygni. Furthermore, two compounds, rubellin E and 14-dehydro rubellin D were isolated and their structures elucidated. In comparison to the other rubellins, rubellin A shows increased photodynamic oxygen activation. By incorporating both [1-(13)C]-acetate and [2-(13)C]-acetate into the rubellins, we showed that such anthraquinone derivatives were biosynthesised via the polyketide pathway. The labelling pattern after being fed [U-(13)C(6)]-glucose proved the existence of fungal folding mode of the poly-beta-keto chain. The ability to produce rubellins is not limited to R. collo-cygni in the anamorph genus Ramularia.