title: Kodaistatins, novel inhibitors of glucose-6-phosphate translocase T1 from Aspergillus terreus thom DSM 11247. Isolation and structural elucidation.
abstract: Two novel compounds, kodaistatin A, C35H34O11, molecular weight 630, and kodaistatin C, C35H34O12, molecular weight 646, have been isolated from cultures of Aspergillus terreus Thom DSM 11247 by solid-phase extraction, size-exclusion chromatography, and various preparative HPLC steps. The use of a range of 2D NMR measurements, in particular 13C-13C correlation measurements, has led to the clarification of the structure of kodaistatin A. Kodaistatin C is a hydroxylated derivative of kodaistatin A. Both natural products contain hydroxylated aspulvinones and identical highly substituted polyketide units. An X-ray single crystal structure analysis of aspulvinon E demonstrated the z-configuration at the central double bond. The kodaistatins are effective inhibitors of the glucose-6-phosphate translocase component of the glucose-6-phosphatase system (EC 3.1.3.9), an enzyme system which is important for the control of blood glucose levels. The IC50 is 80 nM for kodaistatin A and 130 nM for kodaistatin C.
authors.affiliation: Hoechst Marion Roussel Deutschland GmbH, Drug Innovation & Approval, Natural Product Research, Frankfurt/M, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Vértesy
authors.forename: H J
authors.initials: HJ
authors.lastname: Burger
authors.forename: J
authors.initials: J
authors.lastname: Kenja
authors.forename: M
authors.initials: M
authors.lastname: Knauf
authors.forename: H
authors.initials: H
authors.lastname: Kogler
authors.forename: E F
authors.initials: EF
authors.lastname: Paulus
authors.forename: N V
authors.initials: NV
authors.lastname: Ramakrishna
authors.forename: K H
authors.initials: KH
authors.lastname: Swamy
authors.forename: E K
authors.initials: EK
authors.lastname: Vijayakumar
authors.forename: P
authors.initials: P
authors.lastname: Hammann
mesh_terms: D000818:Animals; D017920:Antiporters; D001230:Aspergillus / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D009004:Monosaccharide Transport Proteins; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: D017920:Antiporters; D004791:Enzyme Inhibitors; D007783:Lactones; D009004:Monosaccharide Transport Proteins; C503533:Slc37a4 protein, rat; C414146:aspulvinon E; C111261:glucose 6-phosphate(transporter); C414144:kodaistatin A; C414145:kodaistatin C; D010770:Phosphotransferases