title: Synthesis and antileishmanial activity of new imidazolidin-2-one derivatives.
abstract: N(3)-acyl, arylsulfonyl and benzyl derivatives of N(1)-(4,6-dimethylpyridin-2-yl), (5-methylthiazol-2-yl) or (3-methylisoxazol-5-yl)imidazolidin-2-ones were synthesized and evaluated as potential antileishmanial agents. Determination of their cytotoxic effect was carried out using MRC5 cells. Two compounds, 1-(4,6-dimethylpyridin-2-yl)-3-(napht-2-ylsulfonyl)imidazolidin-2-one, 18, and 1-(3-methylisoxazol-5-yl)-3-(4-bromobenzyl)imidazo-lidin-2-one, 25, exerted significant antileishmanial activity in promastigotes of Leishmania (L) mexicana and Leishmania infantum, with IC(50) in the range of 8-16 micro mol L(-1). Antiparasitical activity of the less toxic compound, 25, was confirmed against intracellular amastigote of L. mexicana, the clinical relevant stage; its low IC(50) value (2.4 micro mol L(-1)) and its favourable toxicity/activity index (11) constitute encouraging results for ongoing pharmacomodulation in the corresponding subseries.
authors.affiliation: Service de Pharmacochimie, UPRES EA 1155, Faculté de Pharmacie, 1, rue Gaston Veil F-44035, Nantes, France. jmrobert@sante.univ-nantes.fr
authors.forename: Jean Michel H
authors.initials: JM
authors.lastname: Robert
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabourin
authors.forename: Nidia
authors.initials: N
authors.lastname: Alvarez
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robert-Piessard
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Baut
authors.forename: Patrice
authors.initials: P
authors.lastname: Le Pape
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002478:Cells, Cultured; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects; D007894:Leishmania mexicana / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D000977:Antiparasitic Agents; D007093:Imidazoles