Table 4.
Drug action analysis of antitrypanosomal compounds by isothermal microcalorimetry
| T. brucei strainb and drug regimen and concn (nM) | Mean (SD) |
Inhibitione (%) | |||
|---|---|---|---|---|---|
| Onset of action (h) | Time to peak (h) | Time to kill (h) | Growth rate (μ) (h−1/1,000) | ||
| STIB900 | |||||
| Drug free | 36 (4) | 119 (13) | 29 (2) | ||
| DB829 | |||||
| 2c | 19 (8)c | 35 (4) | 115 (10) | 28 (1) | 5 |
| 20 | 19 (4) | 32 (3) | 98 (5) | 25 (1) | 15 |
| 200 | 11 (2) | 26 (2) | 77 (13) | 16 (4) | 46 |
| 2,000 | 7 (2) | 17 (4) | 58 (17) | 10 (3) | 66 |
| 20,000 | 5 (1) | 21 (3) | 67 (10) | 8 (3) | 72 |
| Pentamidine | |||||
| 0.2c | 23 (3)c | 39 (6) | 138 (10) | 25 (4) | 12 |
| 2 | 14 (4) | 31 (3) | 89 (14) | 19 (4) | 34 |
| 20 | <4 | 9 (2) | 25 (2) | <1 | ∼98 |
| 200d | <4 | NM | 14 (0) | <1 | ∼98 |
| Melarsoprol | |||||
| 2c | NMa | 40 (5) | 135 (14) | 27 (2) | 3 |
| 20 | 7 (3) | 25 (11) | 107 (56) | 7 (4) | 74 |
| 200d | NM | NM | NM | NM | ∼100 |
| STIB930 | |||||
| Drug free | 53 (2) | 139 (3) | 24 (2) | ||
| DB829 | |||||
| 20c | NM | 51 (4) | 136 (19) | 25 (2) | ∼0 |
| 200 | 26 (7) | 52 (2) | 124 (4) | 23 (1) | 2 |
| 2,000 | 17 (7) | 41 (5) | 99 (11) | 16 (3) | 33 |
| 20,000 | 10 (2) | 41 (2) | 97 (8) | 14 (2) | 43 |
| Pentamidine | |||||
| 0.2c | NM | 53 (2) | 140 (3) | 23 (2) | 4 |
| 2 | 8 (1) | 30 (2) | 75 (8) | 11 (2) | 54 |
| 20b | <4 | 12 (1) | 22 (2) | <1 | ∼96 |
| 200b | <4 | NM | NM | <1 | ∼96 |
| ITMAP141267 | |||||
| Drug free | 58 (4) | 170 (12) | 18 (3) | ||
| DB829 | |||||
| 20c | NM | 57 (5) | 167 (4) | 17 (3) | 6 |
| 200 | 28 (9) | 50 (3) | 124 (7) | 17 (4) | 5 |
| 2,000 | 14 (5) | 33 (12) | 100 (13) | 12 (2) | 33 |
| 20,000 | 12 (5) | 34 (14) | 113 (10) | 10 (2) | 42 |
| Pentamidine | |||||
| 2c | 28 (7) | 57 (2) | 159 (3) | 18 (3) | ∼0 |
| 20 | 6 (1) | 10 (1) | 41 (8) | 3.5 (0.7) | 80 |
| 200 | 4 (1) | 8 (2) | 23 (9) | 1.2 (0.4) | 94 |
a
NM, not measurable.
b
Initial inoculum density was 5 × 104 trypanosomes/ml.
c
Inhibition was too small to accurately recover parameters from every experiment performed.
d
Inhibition was too strong to accurately recover parameters from every experiment performed.
e
Inhibition is measured by the formula [1 − (μdrug/μdrugfree)] × 100.