Pluraflavins, Potent Antitumor Antibiotics from Saccharothrix sp. DSM 12931

• Published in: Journal of antibiotics Vol. 54; no. 9; pp. 718 - 729
• Main Authors: VÉRTESY, LÁSZLÓ, BARBONE, FRANCIS P., CASHMEN, ELIZABETH, DECKER, HEINRICH, EHRLICH, KLAUS, JORDAN, BIRGIT, KNAUF, MARTIN, SCHUMMER, DIETMAR, SEGETH, MARIAN P., WINK, JOACHIM, SEIBERT, GERHARD
• Format: Journal Article
• Language: English
• Published: TOKYO JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 2001; JAPAN ANTIBIOT RES ASSN; Japan Antibiotics Research Association
• Subjects: Actinomycetales - growth & development; Actinomycetales - metabolism; Anthraquinones - chemistry; Anthraquinones - isolation & purification; Anthraquinones - metabolism; Anthraquinones - pharmacology; Antibiotics, Antineoplastic - biosynthesis; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - isolation & purification; Antibiotics, Antineoplastic - pharmacology; Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Antineoplastic agents; Applied microbiology; Biological and medical sciences; Biotechnology & Applied Microbiology; Cell Division - drug effects; Chemotherapic agents; Culture Media; Fundamental and applied biological sciences. Psychology; General aspects; Humans; Immunology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry - methods; Medical sciences; Microbiology; Molecular Structure; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Tumor Cells, Cultured; NMR; SPECTROSCOPY; DNA; ALTROMYCINS; PLURAMYCIN; PROTEINS; COSY; Antineoplastic agent; Flavin derivatives; Carcinoma; NMR spectrometry; Malignant tumor; Fermentation; In vitro; Biological activity; Colonic disease; Fungi; Antibiotic; Structure activity relation; Microorganism culture; Digestive diseases; Intestinal disease; Colon; Tumor cell; Physicochemical properties; Thallophyta; Structural analysis
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.54.718

The new pluramycin-type antibiotics pluraflavin A, C43H54N2O14, pluraflavin B, C43H56N2O15, and pluraflavin E, C36H41NO14 were isolated from cultures of the Saccharothrix species DSM 12931. The structures of the novel compounds were elucidated with the aid of 2D NMR and mass spectrometric investigations. The characteristic structural element of pluraflavins A and B is an additional 4-epi-vancosamine unit at position 13 of the anthraquinone-γ-pyrone ring system. Pluraflavin E has a carboxyl group in this position. Pluraflavin A has a reactive dimethyl epoxide side chain at position 2 of the anthraquinone-γ-pyrone aglycon, which may explain the high activity of the antibiotic. The outstanding biological characteristic of pluraflavin A is its powerful, organ-dependent cytostatic action: the IC50 in the colon carcinoma proliferation assay is in the subnanomolar range.