Table 1.

P. falciparum growth inhibitory activity and effect of IPP supplementation of MMV08138 stereoisomers and D-ring variants.

Entry	Compound	X	P. falciparum Dd2 straina IC50 (nM)	% Rescue (+ 200 μM IPP)b
1	FOS		880 ± 70	100@ 10 μM
2	MMV 008138	2′,4′-Cl2	210 ± 90	100 @ 2.5 μM
3	4a	2′,4′-Cl2	250 ± 70	100 @ 2.5 μM
4	ent-4a	2′,4′-Cl2	>10,000	ND
5	4b	H	>10,000	ND
6	4c	2′-Cl	3,280 ± 990	60 @ 10 μM
7	4d	4′-Cl	1,170 ± 60	50 @ 10 μM
8	4e	2′-Cl, 4′-Me	410 ± 40	100 @ 2.5 μM
9	4f	2′-Me, 4′-Cl	700 ± 90	100 @ 2.5 μM
10	4g	2′,4′-Me2	70% inhibition @ 10,000	ND
11	4h	2′,4′-F2	780 ± 175	100 @ 5 μM
12	4i	2′,4′-(OMe)2	>20,000	ND
13	4j	2′,4′-(CF3)2	>10,000	ND
14	4k	3′,4′-(OMe)2	>20,000	ND
15	5a	2′,4′-Cl2	>10,000	ND
16	ent-5a	2′,4′-Cl2	3,000 ± 200	60 @ 10 μM
17	5b	H	>10,000	ND
18	5e	2′-Cl, 4′-Me	>10,000	ND
19	5g	2′,4′-Me2	>10,000	ND
20	5h	2′,4′-F2	>20,000	ND

^aMRA-150, chloroquine-resistant (intermediate), pyrimethamine-resistant, mefloquine-resistant.

^bDrug at indicated concentration; nd signifies “not determined.”