title: Design, synthesis and biological characterization of thiazolidin-4-one derivatives as promising inhibitors of Toxoplasma gondii.
abstract: We designed and synthesized a large number of novel thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii activity. This scaffold was functionalized at the N1-hydrazine portion with aliphatic, cycloaliphatic and (hetero)aromatic moieties. Then, a benzyl pendant was introduced at the lactamic NH of the core nucleus to evaluate the influence of this chemical modification on biological activity. The compounds were subjected to several in vitro assays to assess their anti-parasitic efficacy, cytotoxicity on fibroblasts, inhibition of tachyzoite invasion/attachment and replication after treatment. Results showed that fourteen of these thiazole-based compounds compare favorably to control compound trimethoprim in terms of parasite growth inhibition.
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: D'Ascenzio
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: bruna.bizzarri@uniroma1.it.
authors.forename: Bruna
authors.initials: B
authors.lastname: Bizzarri
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Celeste
authors.initials: C
authors.lastname: De Monte
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rivanera
authors.affiliation: Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 1105, Baltimore, MD 21287, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Faulhaber
authors.affiliation: Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 1105, Baltimore, MD 21287, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bordón
authors.affiliation: Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 1105, Baltimore, MD 21287, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Jones-Brando
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D053778:Thiazolidines
keywords: Cytotoxicity; Host cell invasion; Parasite growth inhibition; Thiazolidin-4-one; Toxoplasma