Geranylgeraniol-Type Diterpenoids, Boletinins A−J, from Boletinus cavipes as Inhibitors of Superoxide Anion Generation in Macrophage Cells

• Published in: Journal of natural products (Washington, D.C.) Vol. 67; no. 6; pp. 958 - 963
• Main Authors: KAMO, Tsunashi, SATO, Kazuya, SEN, Kikuo, SHIBATA, Hisao, HIROTA, Mitsuru
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.06.2004; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Agaricales - chemistry; Animals; Biological and medical sciences; Chemistry, Medicinal; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - pharmacology; Female; General pharmacology; Japan; Life Sciences & Biomedicine; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Mice; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plant Sciences; Science & Technology; Superoxides - antagonists & inhibitors; Superoxides - metabolism; Japan; HL-60 CELLS; ASSAY; DISMUTASE; Toxicity; Basidiomycetes; Cytotoxicity; Enaldehyde; Medicinal plant; Fungi; Carboxylic acid; Sporophore; Vinylic compound; Radical anion; Inhibition; Acylate; Thallophyta; Terpenoid; Enzyme; Aliphatic compound; Pharmacognosy; Enzyme inhibitor; In vitro; Biological activity; Primary alcohol; Hyperoxides; Polyenic compound; Plant origin; Diterpene; Isolation; Xanthine oxidase; Oxidoreductases; Structural analysis; Macrophage
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np030535g

In addition to 16-hydroxygeranylgeraniol (1) and cavipetin B (2), 10 new geranylgeraniol-type diterpenoids, named boletinins A-J (3-12), were isolated from the fruiting bodies of Boletinus cavipes. Compounds 1-9 and 11 exhibited inhibitory activities of less than 10% at 25-125 muM in the xanthine oxidase test. A bioassay on superoxide anion (O-2(.-)) generation in macrophage cells revealed that 1 and 4-12 suppressed the generation by more than 20% at 25 muM. Compounds 4 and 5 showed inhibitory activities against O-2(.-) generation of more than 50% at 50 muM and exhibited no or low cytotoxicities against macrophage cells at 25-50 muM, suggesting that 4 and 5 are the most promising candidates for O-2(.-) generation inhibitors. O-Acyl geranylgeraniol derivatives, 2 and 7-12, showed cytotoxicities at 25 muM.