Potential Cancer Chemopreventive in Vitro Activities of Monomeric Xanthone Derivatives from the Marine Algicolous Fungus Monodictys putredinis

• Published in: Journal of natural products (Washington, D.C.) Vol. 70; no. 3; pp. 353 - 360
• Main Authors: Krick, Anja, Kehraus, Stefan, Gerhäuser, Clarissa, Klimo, Karin, Nieger, Martin, Maier, Armin, Fiebig, Heinz-Herbert, Atodiresei, Iuliana, Raabe, Gerhard, Fleischhauer, Jörg, König, Gabriele M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.03.2007; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: algae and seaweeds; anticarcinogenic activity; Anticarcinogenic Agents - chemistry; Anticarcinogenic Agents - isolation & purification; Anticarcinogenic Agents - pharmacology; aromatase; Aromatase Inhibitors - chemistry; Aromatase Inhibitors - isolation & purification; Aromatase Inhibitors - pharmacology; Ascomycota; Ascomycota - chemistry; benzophenone; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; chemical analysis; chemical structure; Chemistry, Medicinal; chemoprevention; Crystallography, X-Ray; cultured cells; cytochrome P-450; enzyme inhibition; General pharmacology; Inhibitory Concentration 50; Life Sciences & Biomedicine; Marine Biology; Medical sciences; mice; Molecular Conformation; Molecular Structure; Monodictys putredinis; monodictysin; NAD(P)H Dehydrogenase (Quinone) - biosynthesis; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plant Sciences; Science & Technology; spectral analysis; stereochemistry; Tumors; xanthones; Xanthones - chemistry; Xanthones - isolation & purification; Xanthones - pharmacology; Spain; AGENT; METABOLITES; ACID; CARCINOGENESIS; ASSAY; DIMERS; NAD-(P)-H dehydrogenase (quinone); Benzophenone derivatives; Relative configuration; Estrogen synthase; Anticarcinogen; Fungi; Marine environment; Tissue; Circular dichroism spectrometry; Ascomycetes; Inhibition; Monomer; Thallophyta; Unspecific monooxygenase; Enzyme; Pharmacognosy; Algae; Cytochrome P450; Rodentia; Enzyme inhibitor; Geometrical configuration; In vitro; Biological activity; Vertebrata; Mammalia; Chlorophyta; Mouse; Animal; Absolute configuration; Plant origin; Density functional method; Drug-metabolizing enzyme; Isolation; Oxidoreductases; Structural analysis; Crystalline structure
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np060505o

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 μM. 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 μM, respectively. Compound 3 showed weak inhibition of aromatase activity.