Atropisomeric Dihydroanthracenones as Inhibitors of Multiresistant Staphylococcus aureus

• DOI: 10.1021/jm301816a
• Publication Date: 2013-03-27T14:19:32Z
• Authors: Robert Bara; Ilka Zerfass; Amal H. Aly; Heike Goldbach-Gecke; Vijay Raghavan; Peter Sass; Attila Mándi; Victor Wray; Prasad L. Polavarapu; Alexander Pretsch; WenHan Lin; Tibor Kurtán; Abdessamad Debbab; Heike Brötz-Oeste...; Peter Proksch
• Keywords: Anthracenes; DNA, Bacterial; Staphylococcus aureus; BALB 3T3 Cells; Stereoisomerism; Eurotiales; Microbial Sensitivity Tests; 01 natural sciences; Anti-Bacterial Agents; 0104 chemical sciences; 3. Good health; Mice; Cell Line, Tumor; Drug Resistance, Multiple, Bacterial; Endophytes; Animals; Humans; Aloe; SOS Response, Genetics; Nuclear Magnetic Resonance, Biomolecular

Two bisdihydroanthracenone atropodiastereomeric pairs, including homodimeric flavomannin A (1) and the previously unreported B (2), two new unsymmetrical dimers (3 4), mixed dihydroanthracenone/anthraquinone (5 6) were isolated from Talaromyces wortmannii, an endophyte of Aloe vera. The structures 2–6 elucidated by extensive NMR mass spectrometric analyses. axial chirality biaryls was determined using TDDFT ECD VCD calculations, combination which however did not allow assignment central elements 1. compounds exhibited antibacterial activity against Staphylococcus aureus, (multi)drug-resistant clinical isolates. Reporter gene analyses indicated induction SOS response for some derivatives, suggesting interference with DNA structure or metabolism. Fluorescence microscopy demonstrated defective segregation bacterial chromosome degradation. Notably, showed no cytotoxic activity, encouraging their further evaluation as potential starting points drug development.