Potential cancer chemopreventive in vitro activities of monomeric xanthone derivatives from the marine algicolous fungus Monodictys putredinis.
Investigation of the fungal strain Monodictys putredinis isolated from the inner tissue of a marine green alga led to the isolation of four new monomeric xanthones and a benzophenone. All structures were elucidated by extensive spectroscopic measurements. The relative configuration of compound 1 was determined by X-ray crystal structure analysis, while for 2 and 3 configurations were confirmed by NOE experiments. Absolute configurations for compounds 1-3 were deduced by comparing experimental circular dichroism spectroscopic data with those calculated employing quantum-chemical time-dependent density functional theory (TDDFT). The compounds were examined for their cancer chemopreventive potential. Xanthone 2 was shown to inhibit cytochrome P450 1A activity with an IC50 value of 3.0 microM. Compounds 2 and 3 displayed moderate activity as inducers of NAD(P)H:quinone reductase (QR) in cultured mouse Hepa 1c1c7 cells, with CD values (concentration required to double the specific activity of QR) of 12.0 and 12.8 microM, respectively. Compound 3 showed weak inhibition of aromatase activity.
Krick
Anja
A
Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, D-53115 Bonn, Germany.
Kehraus
Stefan
S
Gerhäuser
Clarissa
C
Klimo
Karin
K
Nieger
Martin
M
Maier
Armin
A
Fiebig
Heinz-Herbert
HH
Atodiresei
Iuliana
I
Raabe
Gerhard
G
Fleischhauer
Jörg
J
König
Gabriele M
GM
D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001203:Ascomycota / Q000737:chemistry*; D018360:Crystallography, X-Ray; D020128:Inhibitory Concentration 50; D008386:Marine Biology; D008968:Molecular Conformation; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D047072:Aromatase Inhibitors; D044004:Xanthones; D016660:NAD(P)H Dehydrogenase (Quinone)