Total synthesis and cytotoxicity evaluation of all ochratoxin A stereoisomers.
The mycotoxin ochratoxin A is a potent inhibitor of the protein biosynthesis and known to be cytotoxic in nanomolar concentrations. In order to investigate the relationship between stereochemistry and cytotoxicity of this compound, all four ochratoxin A stereoisomers have been synthesized. Using the liver cell line Hep G2, the compounds were tested for cytotoxic and apoptotic potential. It could be shown, that the l-configuration of the phenylalanine moiety of the molecule is mostly responsible for the high cytotoxicity of ochratoxin A while the stereocenter at the dihydroisocoumarine structure is of less importance.
Cramer
Benedikt
B
Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 45, 48149 Münster, Germany. cramerb@uni-muenster.de
Harrer
Henning
H
Nakamura
Kazuhiko
K
Uemura
Daisuke
D
Humpf
Hans-Ulrich
HU
D017209:Apoptosis / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D009793:Ochratoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
D003603:Cytotoxins; D009793:Ochratoxins; C025589:ochratoxin A