Table 1.

IC50 of selected lysosomotropic drugs in T. brucei.

The inhibitory concentration (IC50) values of 6 lysosomotropic drugs on bloodstream form T. brucei were measured in this study and compared with those reported in mammalian cells (13, 42, 43). *Note that mammalian IC50 values for CQ, CPZ, PMZ, DSP and 4HT were measured on H9c2 rat-cardiomyocyte-derived cells, whereas mammalian IC50 for LeuLeu-OMe was estimated as the concentration observed to induce necrosis in 8 human cell lines including human neuroblastoma cell line SH-SY5Y, human immortalized keratinocytes HaCaT, human adenocarcinoma cell line HeLa, human hepatoma cell line HepG2, human colon carcinoma cell line CaCo-2, and human embryonic kidney fibroblasts HEK293, human breast carcinoma cell line MCF-7 and normal human dermal fibroblasts, NHDF, cytotoxic T lymphocytes and NK cells. LeuLeu-OMe = L-leucyl-L-leucyl methyl ester; CQ = Chloroquine; CPZ = Chlorpromazine; PMZ = Promethazine; DSP = Desipramine; 4HT = 4-hydroxytamoxifen. The IC50 values for T. brucei were shown as mean (95% confidence interval) from >=4 experiments for each drug.

Drugs	IC50 for T. brucei (µm)	IC50 for mammalian cells* (µm)	Selectivity Index (IC50 mammalian* / IC50 T. brucei)
LeuLeu-OMe	16.8 (14.6-19.4)	125-5000	7.44-298
CQ	29.9 (20.5 - 43.8)	148.3	5
CPZ	9.21 (7.80-10.9)	20.9	2.27
PMZ	13.4 (9.7-18.4)	38.7	2.89
DSP	8.8 (6.37-12.2)	10.7	1.22
4HT	6.23 (3.02-12.8)	6.6	1.06