Constrained peptidomimetics as antiplasmodial falcipain-2 inhibitors.
Herein we report the synthesis of a series of novel constrained peptidomimetics 2-10 endowed with a dipeptide backbone (D-Ser-Gly) and a vinyl ester warhead, structurally related to a previously identified lead compound 1, an irreversible inhibitor of falcipain-2, the main haemoglobinase of lethal malaria parasite Plasmodium falciparum. The new compounds were evaluated for their inhibition against falcipain-2, as well as against cultured P. falciparum. The inhibitory activity of the synthesized compounds was also evaluated against another protozoal cysteine protease, namely rhodesain of Trypanosoma brucei rhodesiense.
Bova
Floriana
F
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.
Ettari
Roberta
R
Micale
Nicola
N
Carnovale
Caterina
C
Schirmeister
Tanja
T
Gelhaus
Christoph
C
Leippe
Matthias
M
Grasso
Silvana
S
Zappalà
Maria
M
D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects / Q000201:enzymology; D014353:Trypanosomiasis, African / Q000188:drug therapy
D000981:Antiprotozoal Agents; D010455:Peptides; D003546:Cysteine Endopeptidases; C416224:falcipain 2; C446033:rhodesain