title: Toxoplasma gondii: inhibitory activity and encystation effect of securinine and pyrrolidine derivatives on Toxoplasma growth.
abstract: Securinine, an alkaloid originally isolated from Securinega suffruticosa, exhibits a wide range of biological activities, including anti-malarial activity. Along with securinine, 10 pyrrolidine derivatives, generated via the retrosynthesis of (-)-securinine, were selected and tested for their inhibitory activity against Toxoplasma gondii growth in vitro. Anti-Toxoplasma activity correlated to hydrophobicity of the tested compounds. Three pyrrolidine derivatives along with securinine inhibit Toxoplasma proliferation at the micromolar range. These compounds act on parasite proliferation in different capacities, either by slowing the growth rate or inhibiting invasion of host cells. Securinine induces bradyzoite differentiation at comparable levels to treatment with alkali media in vitro.
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, Ontario, Canada N9B 3P4.
authors.forename: Michael
authors.initials: M
authors.lastname: Holmes
authors.forename: Anna K
authors.initials: AK
authors.lastname: Crater
authors.forename: Bhartesh
authors.initials: B
authors.lastname: Dhudshia
authors.forename: Avinash N
authors.initials: AN
authors.lastname: Thadani
authors.forename: Sirinart
authors.initials: S
authors.lastname: Ananvoranich
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000469:parasitology; D052816:Foreskin / Q000166:cytology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000494:pharmacology; D006572:Heterocyclic Compounds, Bridged-Ring; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011739:Pyrimethamine / Q000494:pharmacology; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000981:Antiprotozoal Agents; D001381:Azepines; D006576:Heterocyclic Compounds, 4 or More Rings; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D010880:Piperidines; D011759:Pyrrolidines; C000785:securinine; D011739:Pyrimethamine