title: Atropisomeric dihydroanthracenones as inhibitors of multiresistant Staphylococcus aureus.
abstract: Two bisdihydroanthracenone atropodiastereomeric pairs, including homodimeric flavomannin A (1) and the previously unreported flavomannin B (2), two new unsymmetrical dimers (3 and 4), and two new mixed dihydroanthracenone/anthraquinone dimers (5 and 6) were isolated from Talaromyces wortmannii , an endophyte of Aloe vera . The structures of 2-6 were elucidated by extensive NMR and mass spectrometric analyses. The axial chirality of the biaryls was determined using TDDFT ECD and VCD calculations, the combination of which however did not allow the assignment of the central chirality elements of 1. The compounds exhibited antibacterial activity against Staphylococcus aureus , including (multi)drug-resistant clinical isolates. Reporter gene analyses indicated induction of the SOS response for some of the derivatives, suggesting interference with DNA structure or metabolism. Fluorescence microscopy demonstrated defective segregation of the bacterial chromosome and DNA degradation. Notably, the compounds showed no cytotoxic activity, encouraging their further evaluation as potential starting points for antibacterial drug development.
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bara
authors.forename: Ilka
authors.initials: I
authors.lastname: Zerfass
authors.forename: Amal H
authors.initials: AH
authors.lastname: Aly
authors.forename: Heike
authors.initials: H
authors.lastname: Goldbach-Gecke
authors.forename: Vijay
authors.initials: V
authors.lastname: Raghavan
authors.forename: Peter
authors.initials: P
authors.lastname: Sass
authors.forename: Attila
authors.initials: A
authors.lastname: Mándi
authors.forename: Victor
authors.initials: V
authors.lastname: Wray
authors.forename: Prasad L
authors.initials: PL
authors.lastname: Polavarapu
authors.forename: Alexander
authors.initials: A
authors.lastname: Pretsch
authors.forename: WenHan
authors.initials: W
authors.lastname: Lin
authors.forename: Tibor
authors.initials: T
authors.lastname: Kurtán
authors.forename: Abdessamad
authors.initials: A
authors.lastname: Debbab
authors.forename: Heike
authors.initials: H
authors.lastname: Brötz-Oesterhelt
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D000504:Aloe / Q000382:microbiology; D000818:Animals; D000873:Anthracenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D041702:BALB 3T3 Cells; D045744:Cell Line, Tumor; D004269:DNA, Bacterial / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D060026:Endophytes / Q000737:chemistry; D032641:Eurotiales / Q000737:chemistry; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D019906:Nuclear Magnetic Resonance, Biomolecular; D013014:SOS Response, Genetics / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects*; D013237:Stereoisomerism
chemical_list: D000873:Anthracenes; D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial