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ID: ALA1133437

Journal: Bioorg Med Chem Lett

Title: Parallel synthesis of a library of 1,4-naphthoquinones and automated screening of potential inhibitors of trypanothione reductase from Trypanosoma cruzi.

Authors: Salmon-Chemin L, Lemaire A, De Freitas S, Deprez B, Sergheraert C, Davioud-Charvet E.

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.

CiteXplore: 10762041

DOI: 10.1016/s0960-894x(00)00056-1