title: Novel peptidomimetics containing a vinyl ester moiety as highly potent and selective falcipain-2 inhibitors.
abstract: This paper describes the synthesis and biological evaluation of a new class of peptidomimetic falcipain-2 inhibitors based on a 1,4-benzodiazepine scaffold combined with various alpha,beta-unsaturated electrophilic functions such as vinyl-ketone, -amide, -ester, and -nitrile. The profile of reactivity of this class of derivatives has been evaluated and 4c, containing a vinyl ester warhead, proved to be a highly potent and selective falcipain-2 inhibitor.
authors.affiliation: Dipartimento Farmaco-Chimico, University of Messina, Viale Annunziata, Messina, Italy. rettari@pharma.unime.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
authors.forename: Nicola
authors.initials: N
authors.lastname: Micale
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: Emanuela
authors.initials: E
authors.lastname: Nizi
authors.forename: Maria Emilia
authors.initials: ME
authors.lastname: Di Francesco
authors.forename: Silvana
authors.initials: S
authors.lastname: Grasso
authors.forename: Maria
authors.initials: M
authors.lastname: Zappalà
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D020134:Catalytic Domain; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002460:Cell Line; D002463:Cell Membrane Permeability; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004952:Esters; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D004952:Esters; D010455:Peptides; D011994:Recombinant Proteins; D014753:Vinyl Compounds; D001569:Benzodiazepines; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C416224:falcipain 2; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse