Abstract
A decrease in glutathione reductase (GR) activity was observed in Schistosoma mansoni isolated from oltipraz(OPZ)-treated mice. Yeast and Schistosoma mansoni GR-activity was inhibited by OPZ derivatives only. These OPZ-derivatives showed in vitro schistosomicidal activity. Using yeast GR and dithiolium salts of OPZ, time-dependent inactivation and gel chromatography experiments revealed irreversible inhibition dependent on the redox state of the enzyme. Binding of radiolabelled ([ 3H]7-methyl-8-methylthio-pyrrolo[1,2- a]pyrazine disulphide 1b) obtained from OPZ was observed using exclusion chromatography and equilibrium dialysis. These results indicate that GR can be considered as the target of schistosomicidal activity of OPZ. The lack of inhibitory activity of OPZ and dithiole-thione analogues, and the potent activity of the corresponding pyrrolo-pyrazine derivatives, is consistent with the hypothesis that OPZ is a pro-drug.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
