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

Solid- and solution-phase parallel syntheses of 1,4-naphthoquinones (1,4-NQ ) are described. A library of 1360 amides was constructed from the combinat ion of 12 newly synthesised 1,4-NQ carboxylic acid and 120 amines, and was screened for inhibition of trypanothione reductase (TR) from Trypanosoma cr uzi. The most active hits from a primary screening were re-synthesised and confirmed. This approach proves that it is possible to design potent and hi ghly specific TcTR inhibitors deriving From menadione, juglone and plumbagi n. (C) 2000 Elsevier Science Ltd. All rights reserved.