Pluraflavins, potent antitumor antibiotics from Saccharothrix sp. DSM 12931.
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-gamma-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-gamma-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.
Vértesy
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Drug Innovation & Approval, Aventis Pharma Deutschland GmbH, Frankfurt/M, Germany. Laszlo.Vertesy@aventis.com
Barbone
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Cashmen
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Decker
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Ehrlich
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Jordan
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Knauf
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Schummer
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Segeth
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Wink
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Seibert
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D000192:Actinomycetales / Q000254:growth & development / Q000378:metabolism*; D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism* / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D003470:Culture Media; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D014407:Tumor Cells, Cultured
D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; D003470:Culture Media; C440630:pluraflavin A; C440628:pluraflavin B; C440629:pluraflavin E