Table 4.

Activity of amino-artemisinins against P. falciparum asexual blood stage artemisinin-resistant clones carrying the Pf KI3 C580Y mutation as determined with the T₀ [³H]-hypoxanthine drug susceptibility assay.

Compounda	W2		ARC08-22 (4G) (48 h lc)b			PL08-009 (5C) (36 h lc)b
	IC50 nM	IC90 nM	IC50 nM	IC90 nM	RIc	IC50 nM	IC90 nM	RId
DHA 2	4.58 ± 2.54	10.30 ± 5.76	6.68 ± 0.61	15.40 ± 1.39	1.5	6.41 ± 1.54	10.73 ± 3.81	1.4
Artemiside 7	2.21 ± 0.42	4.28 ± 0.25	2.43 ± 0.13	4.85 ± 0.09	1.1	0.29 ± 0.03	0.43 ± 0.03	0.1
Artemisone 8	1.69 ± 0.36	3.42 ± 0.45	1.62 ± 0.19	3.38 ± 0.28	1.0	0.27 ± 0.05	0.43 ± 0.07	0.2
Urea 10	0.12 ± 0.03	0.20 ± 0.03	0.19 ± 0.02	0.36 ± 0.03	1.6	4.71 ± 0.60	6.45 ± 1.81	39.3
Sulfamide 11	4.87 ± 0.59	7.53 ± 0.23	4.76 ± 0.25	7.55 ± 0.26	1.0	1.81 ± 0.20	2.38 ± 0.06	0.4
Arylamine 12	4.76 ± 0.38	8.51 ± 0.34	5.51 ± 0.59	10.92 ± 0.95	1.2	15.73 ± 0.72	22.57 ± 1.00	3.3
DHA piperazine amides
27	0.21 ± 0.04	0.41 ± 0.08	0.39 ± 0.02	0.70 ± 0.05	1.9	9.49 ± 1.05	14.06 ± 1.27	45.2
28	0.10 ± 0.03	0.19 ± 0.02	0.16 ± 0.01	0.43 ± 0.02	1.6	4.22 ± 0.42	5.83 ± 1.37	42.2

^aStructures in Figures 1, 2 and Scheme 1.

^blc = life cycle (h).

^cRI = IC₅₀ for ARC08-22(4G)/IC₅₀ for W2.

^dRI = IC₅₀ for PL08-09 (5C)/ IC₅₀ for W2. Results are the mean of three independent biological replicates, performed as technical triplicates, ±SEM.