title: Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents.
abstract: Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50=5.29μM), coupled with a lack of cytotoxicity towards mammalian cells (TC50 >100μM).
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Santo
authors.initials: S
authors.lastname: Previti
authors.affiliation: DiSTABiF, Second University of Naples, Via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Santina
authors.initials: S
authors.lastname: Maiorana
authors.affiliation: Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55099 Mainz, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Grasso
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina, Italy. Electronic address: mzappala@unime.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Zappalà
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D008264:Macrophages; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D014344:Trypanocidal Agents; D001569:Benzodiazepines; C468549:Bz-423
keywords: Michael acceptors; Microwave irradiation; Peptidomimetics; Pharmacokinetic parameters; Trypanosoma