Anthraquinones and betaenone derivatives from the sponge-associated fungus Microsphaeropsis species: novel inhibitors of protein kinases.
An undescribed fungus of the genus Microsphaeropsis, isolated from the Mediterranean sponge Aplysina aerophoba, produces two new betaenone derivatives (1, 2) and three new 1,3,6, 8-tetrahydroxyanthraquinone congeners (5-7). The structures of the compounds were established on the basis of NMR spectroscopic and mass spectrometric data and by CD spectroscopy. This is the first report wherein the (1)H and (13)C NMR data of the betaenone congeners are fully and unambiguously assigned on the basis of two-dimensional NMR spectroscopy. Furthermore, we describe the first elucidation of the absolute configuration of 1-(2'-anthraquinonyl)ethanols such as 5 and 6, by quantum chemical calculation of their circular dichroism (CD) and comparison with experimentally measured spectra. Moreover, it was shown that compounds 1, 5, 6, and 7 are inhibitors of PKC-epsilon, CDK4, and EGF receptor tyrosine kinases.
Brauers
G
G
Heinrich-Heine-Universität, Lehrstuhl für Pharmazeutische Biologie, Universitätsstrasse 1, Geb. 26.23, D-40225 Düsseldorf, Germany.
Edrada
R A
RA
Ebel
R
R
Proksch
P
P
Wray
V
V
Berg
A
A
Gräfe
U
U
Schächtele
C
C
Totzke
F
F
Finkenzeller
G
G
Marme
D
D
Kraus
J
J
Münchbach
M
M
Michel
M
M
Bringmann
G
G
Schaumann
K
K
D000818:Animals; D000880:Anthraquinones / Q000737:chemistry*; D002942:Circular Dichroism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D007659:Ketones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D003904:Mitosporic Fungi / Q000737:chemistry*; D009284:Naphthols / Q000737:chemistry*; D011161:Porifera / Q000382:microbiology*; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors
D000880:Anthraquinones; D004791:Enzyme Inhibitors; D007659:Ketones; D009284:Naphthols; D047428:Protein Kinase Inhibitors