title: Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors.
abstract: Novel rhodesain inhibitors were developed by combining an enantiomerically pure 3-bromoisoxazoline warhead with a 1,4-benzodiazepine scaffold as specific recognition moiety. All compounds were proven to inhibit rhodesain with Ki values in the low-micromolar range. Their activity towards rhodesain was found to be coupled to an in vitro antitrypanosomal activity, with IC50 values ranging from the mid-micromolar to a low-micromolar value for the most active rhodesain inhibitor (R,S,S)-3. All compounds showed a good selectivity against the target enzyme since all of them were proven to be poor inhibitors of human cathepsin L.
authors.affiliation: a Dipartimento Di Scienze Del Farmaco E Dei Prodotti per La Salute , University of Messina , Messina , Italy .
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
authors.affiliation: a Dipartimento Di Scienze Del Farmaco E Dei Prodotti per La Salute , University of Messina , Messina , Italy .
authors.forename: Santo
authors.initials: S
authors.lastname: Previti
authors.affiliation: b DiSTABiF , Second University of Naples , Naples , Italy .
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.affiliation: c Institute of Pharmacy and Biochemistry, University of Mainz , Mainz , Germany , and.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kesselring
authors.affiliation: c Institute of Pharmacy and Biochemistry, University of Mainz , Mainz , Germany , and.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.affiliation: d Dipartimento Di Scienze Chimiche , University of Messina , Messina , Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Grasso
authors.affiliation: a Dipartimento Di Scienze Del Farmaco E Dei Prodotti per La Salute , University of Messina , Messina , Italy .
authors.forename: Maria
authors.initials: M
authors.lastname: Zappalà
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D057786:Peptidomimetics / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D057786:Peptidomimetics; D003546:Cysteine Endopeptidases; C446033:rhodesain
keywords: Peptidomimetics; rhodesain; trypanosoma