New natural products from the sponge-derived fungus Aspergillus niger.
Fractionation of the EtOAc extract of a static culture of Aspergillus niger isolated from the Mediterranean sponge Axinella damicornis yielded eight secondary metabolites, out of which seven compounds (2-8) proved to be new natural products, whereas one was identified as the known fungal pigment cycloleucomelone (1). The new compounds included the 3,3'-bicoumarin bicoumanigrin (2), the structurally unusual 4-benzyl-1H-pyridin-6-one derivatives aspernigrins A and B (3 and 4), and pyranonigrins A-D (5-8), the latter featuring a novel pyrano[3,2-b]pyrrole skeleton hitherto unprecedented in nature. All structures were elucidated on the basis of extensive one- and two-dimensional NMR spectroscopic studies ((1)H, (13)C, COSY, HMQC, HMBC, NOE difference spectra) and mass spectral analysis. For the two chiral molecules 4 and 5, the absolute configurations were established by quantum chemical calculations of their circular dichroism (CD) spectra. In each case, two independent methods, i.e., a molecular dynamics approach taking into consideration the molecular flexibility, and a conformational analysis followed by Boltzmann weighting of the single CD spectra calculated for the conformers thus obtained, led to identical results without the need of any empirical comparison of chiroptical data reported for reference compounds. Bicoumanigrin (2) showed moderate cytotoxicity against human cancer cell lines in vitro. In addition, aspernigrin B (4) was found to display a strong neuroprotective effect against glutamic acid.
Hiort
J
J
Institut für Pharmazeutische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, Geb. 26.23., D-40225 Düsseldorf, Germany.
Maksimenka
K
K
Reichert
M
M
Perović-Ottstadt
S
S
Lin
W H
WH
Wray
V
V
Steube
K
K
Schaumann
K
K
Weber
H
H
Proksch
P
P
Ebel
R
R
Müller
W E G
WE
Bringmann
G
G
D000818:Animals; D001234:Aspergillus niger / Q000737:chemistry*; D002118:Calcium / Q000032:analysis; D002942:Circular Dichroism; D004354:Drug Screening Assays, Antitumor; D018698:Glutamic Acid / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D008522:Mediterranean Sea; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D006571:Heterocyclic Compounds; D018698:Glutamic Acid; D002118:Calcium