title: Cell permeation of a Trypanosoma brucei aldolase inhibitor: evaluation of different enzyme-labile phosphate protecting groups.
abstract: A series of four prodrugs directed against Trypanosoma brucei aldolase bearing various transient enzyme-labile phosphate protecting groups was developed. Herein, we describe the synthesis and evaluation of cell permeation of these prodrugs. The oxymethyl derivative was the most efficient prodrug with a good recovering of the free drug (IC(50)=20 microM) and without any measurable cytotoxicity.
authors.affiliation: Laboratoire SPCMIB, Groupe de Chimie Organique Biologique, Université Paul Sabatier UMR CNRS 5068, 118 route de Narbonne, 31062 Toulouse Cedex 4, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Azéma
authors.forename: Christian
authors.initials: C
authors.lastname: Lherbet
authors.forename: Cécile
authors.initials: C
authors.lastname: Baudoin
authors.forename: Casimir
authors.initials: C
authors.lastname: Blonski
mesh_terms: D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors*; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D010755:Organophosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D010755:Organophosphates; D011355:Prodrugs; D000446:Aldehyde-Lyases