title: Polyamine-trypanothione pathway: an update.
abstract: In trypanosomatids, polyamine and trypanothione pathways can be considered as a whole unique metabolism, where most enzymes are essential for parasitic survival and infectivity. Leishmania parasites and all the other members of the Trypanosomatids family depend on polyamines for growth and survival: the enzymes involved in the synthesis and utilization of spermidine and trypanothione, i.e., arginase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, spermidine synthase and in particular trypanothione synthetase-amidase, trypanothione reductase and tryparedoxin-dependent peroxidase are promising targets for drug development. This review deals with recent structure-based studies on these enzymes, aimed at the discovery of inhibitors of this pathway.
authors.affiliation: CNR - National Research Council of Italy, Institute of Molecular Biology & Pathology, c/o Department of Biochemical Sciences "A. Rossi Fanelli", University Sapienza, P.le Aldo Moro 5, 00185 - Rome, Italy.|Istituto Pasteur Fondazione Cenci-Bolognetti c/o Department of Biochemical Sciences "A. Rossi Fanelli", University Sapienza, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ilari
authors.affiliation: CNR - National Research Council of Italy, Institute of Molecular Biology & Pathology, c/o Department of Biochemical Sciences "A. Rossi Fanelli", University Sapienza, P.le Aldo Moro 5, 00185 - Rome, Italy.|Department of Biochemical Sciences "A. Rossi Fanelli", University Sapienza, Rome, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Fiorillo
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", University Sapienza, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Genovese
authors.affiliation: CNR - National Research Council of Italy, Institute of Molecular Biology & Pathology, c/o Department of Biochemical Sciences "A. Rossi Fanelli", University Sapienza, P.le Aldo Moro 5, 00185 - Rome, Italy.|Istituto Pasteur Fondazione Cenci-Bolognetti c/o Department of Biochemical Sciences "A. Rossi Fanelli", University Sapienza, Rome, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Colotti
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D053898:Biosynthetic Pathways / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007896:Leishmaniasis / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D015394:Molecular Structure; D011073:Polyamines / Q000378:metabolism*; D013095:Spermidine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D011073:Polyamines; C044809:trypanothione; D005978:Glutathione; D013095:Spermidine
keywords: Leishmania; drug discovery; polyamines; trypanothione pathway