Jugiones A-D: Antibacterial Xanthone-Anthraquinone Heterodimers from Australian Soil-Derived CMB-STF067.

The Australian roadside soil-derived fungus CMB-STF067 was prioritized for chemical investigation based on an SDA cultivation extract exhibiting both antibacterial properties and natural products with unprecedented molecular formulae (GNPS). Subsequent miniaturized 24-well plate cultivation profiling (MATRIX) identified red rice as optimal for the production of the target chemistry, with scaled-up cultivation, extraction and fractionation yielding four new xanthone-anthraquinone heterodimers, jugiones A-D (-), whose structures were assigned by detailed spectroscopic analysis and biosynthetic considerations. Of note, where - and were active against the Gram-positive bacteria vancomycin-resistant (IC 2.6-3.9 μM) and multiple-drug-resistant clinical isolates of (IC 1.8-6.4 μM), and inactive against the Gram-negative bacteria (IC > 30 μM), the closely related analog exhibited no antibacterial properties (IC > 30 μM). Furthermore, where was cytotoxic to human carcinoma (IC 9.0-9.8 μM) and fungal (IC 4.1 μM) cells, and displayed no such cytotoxicity (IC > 30 μM), revealing an informative structure activity relationship (SAR). We also extended the SAR study to other known compounds of this heterodimer class, which showed that the modification of ring G can reduce or eliminate the cytotoxicity while retaining the antibacterial activity.