Table 3. Compounds enhancing tritryp trypanothione synthetase (TryS) activity.
| Compound | Core structurea | TcTryS | LiTryS | TbTryS |
|---|---|---|---|---|
| ZVR159 | APPDA | 168.6 ± 4.1; (1.10) | 100.6 ± 5.8 | 81.3 ± 1.6 |
| AD81 | BBHPP | 109.7 ± 8.9 | 83.9 ± 4.2 | 128.2 ± 3.6; (0.93) |
| AD84 | BBHPP | 98.7 ± 5.1 | 82.1 ± 4.0 | 119.0 ± 6.3; (0.95) |
| ADMRC158 | BBHPP | 97.4 ± 6.1 | 85.3 ± 8.7 | 119.1 ± 4.6; (0.88) |
| ADPKN160 | BBHPP | 97.6 ± 3.7 | 77.9 ± 3.6 | 116.4 ± 4.2; (0.87) |
| ADPKN161 | BBHPP | 90.8 ± 5.8 | 83.5 ± 9.2 | 126.7 ± 0.8; (0.86) |
| ADPKN164 | BBHPP | 99.6 ± 5.7 | 66.0 ± 3.4 | 123.2 ± 7.0; (0.83) |
| ADPKN165 | BBHPP | 107.1 ± 4.5 | 83.5 ± 6.0 | 166.3 ± 5.5; (0.79) |
| J20 | BZ | 64.4 ± 3.8 | 111.5 ± 14.5; (0.97) | 118.8 ± 2.4; (0.97) |
| J31 | BZ | 118.8 ± 6.1; (1.00) | 84.1 ± 0.001 | 96.2 ± 3.7 |
| TC227 | PD | 161.6 ± 5.3; (0.98) | 88.5 ± 7.1 | 102.0 ± 2.3 |
Enzyme activity is expressed as % TryS activity ± 2σn-1 and in brackets is provided the interference factor used to correct TryS activity of compounds affecting BIOMOL GREEN signal (see S1 Text). All values reported stem from at least triplicates. TcTryS, TbTryS and LiTryS are the trypanothione synthetase of Trypanosoma cruzi, Trypanosoma brucei and Leishmania infantum, respectively. ND, not determined.
a the chemical scaffolds are: APPDA, 6-arylpyrido[2,3-d]pyrimidine-2,7-diamine derivative; BBHPP, 1-(benzo[d]thiazol-2-yl)-4-benzoyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-one derivatives; BZ, benzofuroxan derivatives; PD, 1H-purine-2,6(3H,7H)-dione derivative.