Table 1.

EC₅₀ values [μm] against trypomastigotes of T. b. brucei (T. b. b.), T. congolense (T. c.), and HFF cells, along with selectivity indexes, resistance factors, and predicted logP values for compounds 8–22.

Compd	T. b. b. 427WT	SI[a]	T. b. b. B48	RF[b]	T. b. b. aqp2/aq3‐KO	RF[b]	T. c. IL3000 WT	HFF[c]	logP [d]
8	>200		n.d.		n.d.		n.d.	n.d.	10.88
9	>200		n.d.		n.d.		n.d.	n.d.	10.85
10	>200		n.d.		n.d.		n.d.	n.d.	10.85
11	>200		n.d.		n.d.		n.d.	n.d.	11.07
12	>200		n.d.		n.d.		n.d.	n.d.	11.07
13	>200		n.d.		n.d.		n.d.	n.d.	10.75
14	>200		n.d.		n.d.		n.d.	n.d.	11.0
15	>200		n.d.		n.d.		n.d.	n.d.	11.0
16	>200		n.d.		n.d.		n.d.	n.d.	11.22
17	>200		n.d.		n.d.		n.d.	n.d.	11.22
18	9.1±1.4	>21.98	8.6±2.4	0.95	10.1±2.2	1.1	n.d.	n.e.	5.64
19	15.0±1.3	>13.3	14.6±1.7	0.98	17.7±1.5	1.2	n.d.	n.e.	5.62
20	5.0±0.3	>40	5.3±0.8	1.1	6.2±0.58	1.2	18.8±0.2	n.e.	5.62
21	40.5±4.9	>5	36.9±5.3	0.91	46.7±7.7	1.2	n.d.	n.e.	5.84
22	7.6±0.7	>26.3	6.8±0.1	0.91	7.3±0.5	0.96	43.4±0.2	n.e.	5.84
4	48.7±0.8	n.d.	63.0±0.4	1.3	62.4±0.8	1.3	108±2	n.d.[g]	n.d.
PMD[e]	0.0093±0.0001		3.1±0.7	339	0.20±0.01	22.0	n.d.	n.d.	n.d.
DA[f]	n.d.		n.d.		n.d.		0.17±0.0003	n.d.	n.d.

None of the EC₅₀ values for the test compounds against the T. b. b. 427WT strain were significantly different in the B48 or aqp2/aqp3‐KO strains. In contrast, the EC₅₀ value for pentamidine (PMD) was highly significantly different in the latter two strains relative to 427WT (p<0.001, Student's unpaired t‐test, n=4 for all data points); n.d.: not determined; n.e.: no effect at 200 μm. [a] Selectivity index=EC₅₀(HFF)/EC₅₀(T. b. b. WT). [b] Resistance factor relative to WT. [c] Cytotoxic activity (EC₅₀) on human foreskin fibroblast (HFF) cells; cytotoxic activity was observed up to 200 μm. [d] logP values were predicted with FAFDrugs4 software (http://fafdrugs3.mti.univ‐paris‐diderot.fr). [e] Pentamidine. [f] Diminazene aceturate. [g] The EC₅₀ value of 4 is 9.84±3.25 against human dermal fibroblasts (HDF).14c