Table 3.

Potency and Selectivity of VS Inhibitors Designed to Optimize Capping Group and Solubility^a,b

No.	Cap	R3	R2	R1	72 h EC50 (μM)			1 h EC50 (μM)
					Pf	HFF	SI	Pf	HFF	SI
18					0.034 ± 0.006	13.63 ±2.63	402	0.384 ±0.071	>250
19					0.009 ± 0.0059	1.7 ± 0.26	187	0.155 ± 0.060	54.3 ±11.2	349
20					nd	nd	nd	nd	nd	nd
21					0.013 ± 0.004	2.75 ± 0.50	212	0.251 ± 0.027	95.3 ± 15.3	379
22					nd	nd	nd	nd	nd	nd
23					0.003 ± 0.0007	2.22 ±0.077	716	0.048 ±0.009	>250
24					0.002 ± 0.0004	0.727 ±0.092	346	0.012 ± 0.003	28.73 ±5.65	2355
25					0.004 ± 0.0007	0.985 ±0.093	281	0.021 ± 0.004	18.66 ±2.95	906
26					0.007 ± 0.002	3.45 ± 0.30	493	0.042 ±0.001	113 ±23.3	2690
27					0.072 ± 0.008	73.39 ±7.21	1016	>2.5	>250
28					0.019 ± 0.003	29.67 ± 4.45	1561	0.648 ± 0.099	>250
29					0.009 ±0.001	23.13 ± 3.53	2559	1.065 ± 0.242	>250
30					0.005 ±0.001	0.061 ±0.008	11.43	0.121 ± 0.032	42.45 ±7.7	351

^aEC₅₀ values for inhibitors 18–30 in 72 and 1 h treatment of P. falciparum W2 at ring stage parasites and non-confluent HFFs.

^bSI, selectivity index; nd, not determined.