Highly tunable thiosulfonates as a novel class of cysteine protease inhibitors with anti-parasitic activity against Schistosoma mansoni.
Bioorg Med Chem
; 27(13): 2857-2870, 2019 07 01.
Article
de En
| MEDLINE
| ID: mdl-31126821
ABSTRACT
The development of a new class of cysteine protease inhibitors utilising the thiosulfonate moiety as an SH specific electrophile is described. This moiety has been introduced into suitable amino acid derived building blocks, which were incorporated into peptidic sequences leading to very potent i.e. sub micromolar inhibitors of the cysteine protease papain in the same range as the vinyl sulfone based inhibitor K11777. Therefore, their inhibitory effect on Schistosoma mansoni, a human blood parasite, that expresses several cysteine proteases, was evaluated. The homophenylalanine side chain containing compounds 27-30 and especially 36 showed promising activities compared with K11777 and warrant further investigations of these peptidic thiosulfonate inhibitors as new potential anti-parasitic compounds.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Schistosoma mansoni
/
Acides thiosulfoniques
/
Inhibiteurs de la cystéine protéinase
Limites:
Animals
Langue:
En
Journal:
Bioorg Med Chem
Sujet du journal:
BIOQUIMICA
/
QUIMICA
Année:
2019
Type de document:
Article
Pays d'affiliation:
Royaume-Uni