Identification of Novel Chemical Scaffolds Inhibiting Trypanothione Synthetase from Pathogenic Trypanosomatids
Fig 3
The different steps, the most relevant assay conditions and the go/no-go criteria of the screening campaign are indicated in boxes. The figures on the right refer to the number of compounds screened and that subsequently advanced during the campaign. From 144 compounds, 22 compounds lowered assay signal ≥ 45% for at least one TryS. From these 22, 7 BDA were false positive and the remaining 15 compounds were confirmed as enzyme inhibitors. Two of them are AI with potency in the submicromolar range against LiTryS. AI (P), 4,5-dihydroazepino[4,5-b]indol-2(1H,3H,6H)-one derivatives (P, paullone); APPDA, 6-arylpyrido[2,3-d]pyrimidine-2,7-diamine derivatives; BZ, benzofuroxan derivatives; BDA, N,N'-bis(3,4-substituted-benzyl) diamine derivatives.
