Polyketides from the marine-derived fungus Ascochyta salicorniae and their potential to inhibit protein phosphatases.
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.
Seibert
Simon F
SF
Institute for Pharmaceutical Biology, University of Bonn, D-53115 Bonn, Germany.
Eguereva
Ekaterina
E
Krick
Anja
A
Kehraus
Stefan
S
Voloshina
Elena
E
Raabe
Gerhard
G
Fleischhauer
Jörg
J
Leistner
Eckhard
E
Wiese
Michael
M
Prinz
Heino
H
Alexandrov
Kirill
K
Janning
Petra
P
Waldmann
Herbert
H
König
Gabriele M
GM
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*
D004791:Enzyme Inhibitors; D018942:Macrolides; D010749:Phosphoprotein Phosphatases