Antiprotozoal glutathione derivatives with flagellar membrane binding activity against T. brucei rhodesiense

Daunes, Sylvie; Yardley, Vanessa; Croft, Simon L.; D’Silva, Claudius

doi:10.1016/j.bmc.2016.12.016

Cited by 2 publications

(1 citation statement)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most GSH-dependent enzymes have proved to be pharmacological targets for anticancer [ 6 , 7 ] and antiparasitic [ 8 , 9 , 10 ] agents such as GSH derivatives and mimetics with enzyme inhibitory activity. The redox properties of GSH per se have attracted great interest in the therapy of degenerative, inflammatory, immunological and viral diseases accompanied by oxidative stress and thiol depletion in cells [ 3 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione

et al. 2021

View full text Add to dashboard Cite

Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, a vital tripeptide with antioxidant, protective and regulatory functions. DTP moiety imparted radical scavenging activity to oxidized glutathione (GSSG), modulated the activity of reduced glutathione (GSH) and profoundly improved adsorption and electrooxidation of both glutathione salts on graphene oxide modified electrode. According to NMR spectroscopy and GC–MS, the dithiophosphates persisted against immediate dissociation in an aqueous solution accompanied by hydrolysis of DTP moiety into phosphoric acid, menthol and hydrogen sulfide as well as in situ thiol-disulfide conversions in peptide moieties due to the oxidation of GSH and reduction of GSSG. The thiol content available in dissolved GSH dithiophosphate was more stable during air oxidation compared with free GSH. GSH and the dithiophosphates, unlike DTP, caused a thiol-dependent reduction of MTS tetrazolium salt. The results for the first time suggest O,O-dimenthyl DTP as a redox modifier for glutathione, which releases hydrogen sulfide and induces biorelevant redox conversions of thiol/disulfide groups.

show abstract