TABLE 1.
Sensitivities and sterol composition of T. brucei cells to silencing TbSMT or TbSDM and ergosterol biosynthesis inhibitors
| Treatment | PCFa (μM) | BSFa (μM) | HEKa (μM) | TIb | Sterol Composition (% Total)c | |||
| Cholesterol | 24-Desalkyl Sterols | 24-Alkyl Sterols | Ergd | |||||
| Control | ND | ND | ND | ND | 51 | 40 | 9 | 3.5 |
| RNAi TbSMT | ND | ND | ND | ND | 76 | 24 | Trace | 0.3 |
| RNAi TbSDM | ND | ND | ND | ND | 83 | 12 | 5 | 0.3 |
| AZA | 1 | 2 | >50 | 25 | 90 | 10 | Trace | NP |
| 25-Thialanosterol sulfonium salt | 2 | 2 | >50 | 25 | 92 | 7 | Trace | NP |
| ITC | 3 | 3 | >100 | 33 | 87 | 4 | 9 | NP |
TI, therapeutic index; Erg, ergosterol; ND, not determined; NP, not present within routine limits of detection by GC-MS analysis.
The values were calculated from the dose-response curves of cultures in FGM. The dose causing a 50% cell growth inhibition, ED50 <10 μM being proposed as a threshold to consider a compound as a potential antisleeping sickness drug (45).
Therapeutic index ED50 HEK/ED50 BSF. Each value is a mean of three independent experiments which varied by 0.2–0.3 μM.
Sterol composition of DOX-induced RNAi cell lines and treated cells at ED90 drug concentration; trace is <1% total sterol.
Ergosterol content in the total sterols.