title: Polyketides from the marine-derived fungus Ascochyta salicorniae and their potential to inhibit protein phosphatases.
abstract: Chemical investigation of the marine fungus Ascochyta salicorniae led to the isolation of two new epimeric compounds, ascolactones A (1) and B (2), in addition to the structurally-related polyketides hyalopyrone (3), ascochitine (4), ascochital (5) and ascosalipyrone (6). The absolute configurations of the epimeric compounds 1 and 2 were assigned as (1R,9R) and (1S,9R), respectively, through simulation of the chiroptical properties using quantum-chemical CD calculations, and chiral GC-MS subsequent to oxidative cleavage (Baeyer-Villiger oxidation) of the side chain. In silico screening using the PASS software identified some of the A. salicorniae compounds (1-6) as potential inhibitors of protein phosphatases. Compound was found to inhibit the enzymatic activity of MPtpB with an IC(50) value of 11.5 microM.
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, D-53115 Bonn, Germany.
authors.forename: Simon F
authors.initials: SF
authors.lastname: Seibert
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Eguereva
authors.forename: Anja
authors.initials: A
authors.lastname: Krick
authors.forename: Stefan
authors.initials: S
authors.lastname: Kehraus
authors.forename: Elena
authors.initials: E
authors.lastname: Voloshina
authors.forename: Gerhard
authors.initials: G
authors.lastname: Raabe
authors.forename: Jörg
authors.initials: J
authors.lastname: Fleischhauer
authors.forename: Eckhard
authors.initials: E
authors.lastname: Leistner
authors.forename: Michael
authors.initials: M
authors.lastname: Wiese
authors.forename: Heino
authors.initials: H
authors.lastname: Prinz
authors.forename: Kirill
authors.initials: K
authors.lastname: Alexandrov
authors.forename: Petra
authors.initials: P
authors.lastname: Janning
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: König
mesh_terms: D001203:Ascomycota / Q000737:chemistry*; D002942:Circular Dichroism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D018942:Macrolides; D010749:Phosphoprotein Phosphatases