Isoaurostatin, a Novel Topoisomerase Inhibitor Produced by Thermomonospora alba

• Published in: Journal of natural products (Washington, D.C.) Vol. 64; no. 2; pp. 204 - 207
• Main Authors: SUZUKI, Keitarou, YAHARA, Shoji, MAEHATA, Kazutomo, UYEDA, Masaru
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.02.2001; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: 6,4'-Dihydroxyisoaurone; Actinomycetales - chemistry; Animals; Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Applied microbiology; Benzofurans - isolation & purification; Benzofurans - pharmacology; Biological and medical sciences; Cattle; Chemistry, Medicinal; Chemotherapic agents; DNA Topoisomerases, Type II - metabolism; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; isoaurostatin; Kinetics; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Microbiology; Models, Chemical; Pharmacology & Pharmacy; Placenta - enzymology; Plant Sciences; Protein Conformation; Science & Technology; Thermomonospora alba; Thymus Gland - enzymology; Topoisomerase I Inhibitors; topoisomerase inhibitors; TOPOSTATIN; BREAKAGE-REUNION REACTION; STRAIN-NO-1520; MECHANISM; BINDING; DNA; Ox; Oxygen heterocycle; Actinomycetales; Isomerases; Bicyclic compound; Bacteria; Aromatic compound; Ungulata; Thermomonospora; Vegetals; Thymus gland; Enzyme; Micromonosporaceae; DNA topoisomerase; Calf; Filtrate; Enzyme inhibitor; Wheat germ; Lactone; In vitro; Biological activity; Vertebrata; Mammalia; Animal; Phenols; Benzenic compound; Non competitive inhibition; Isolation; Actinomycetes; Artiodactyla; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np0004606

A novel inhibitor of topoisomerase I designated as isoaurostatin (1) was isolated from the culture filtrate of Thermomonospora alba strain No. 1520. The structure of 1 was determined to be 6,4'-dihydroxyisoaurone on the basis of spectroscopic (NMR and MS) methods. Compound 1 inhibited the relaxation activity of calf thymus topoisomerase I in a noncompetitive manner and did not inhibit the relaxation and decatenation of human placenta topoisomerase II. Compound 1 is an inhibitor belonging to cleavable complex-nonforming type without DNA intercalation.