title: Parallel synthesis of a library of 1,4-naphthoquinones and automated screening of potential inhibitors of trypanothione reductase from Trypanosoma cruzi.
abstract: Solid- and solution-phase parallel syntheses of 1,4-naphthoquinones (1,4-NQ) are described. A library of 1360 amides was constructed from the combination of 12 newly synthesised 1,4-NQ carboxylic acid and 120 amines, and was screened for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi. The most active hits from a primary screening were re-synthesised and confirmed. This approach proves that it is possible to design potent and highly specific TcTR inhibitors deriving from menadione, juglone and plumbagin.
authors.affiliation: UMR 8525 CNRS, Université Lille II, Institut de Biologie de Lille, Institut Pasteur de Lille, France.
authors.forename: L
authors.initials: L
authors.lastname: Salmon-Chemin
authors.forename: A
authors.initials: A
authors.lastname: Lemaire
authors.forename: S
authors.initials: S
authors.lastname: De Freitas
authors.forename: B
authors.initials: B
authors.lastname: Deprez
authors.forename: C
authors.initials: C
authors.lastname: Sergheraert
authors.forename: E
authors.initials: E
authors.lastname: Davioud-Charvet
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001331:Automation; D004353:Drug Evaluation, Preclinical / Q000379:methods; D020128:Inhibitory Concentration 50; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011786:Quality Control; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; C035342:1,4-naphthoquinone