title: Constrained peptidomimetics as antiplasmodial falcipain-2 inhibitors.
abstract: 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.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Bova
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
authors.forename: Nicola
authors.initials: N
authors.lastname: Micale
authors.forename: Caterina
authors.initials: C
authors.lastname: Carnovale
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.forename: Christoph
authors.initials: C
authors.lastname: Gelhaus
authors.forename: Matthias
authors.initials: M
authors.lastname: Leippe
authors.forename: Silvana
authors.initials: S
authors.lastname: Grasso
authors.forename: Maria
authors.initials: M
authors.lastname: Zappalà
mesh_terms: 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
chemical_list: D000981:Antiprotozoal Agents; D010455:Peptides; D003546:Cysteine Endopeptidases; C416224:falcipain 2; C446033:rhodesain