Table 3.

Growth Inhibition (P. falciparum, E. coli) and Pf IspD Inhibition of C3-Carboxy Replacement Variants of 1a

compounda	X	P. falciparum growth inhibition IC50 (nM)b	% recovery (200 μM IPP)d	PfIspD IC50 (nM)e	% E. coli growth inhibition (18 h)f
3a	2′,4′-Cl2	6800 ± 1400c	20 ± 10 @ 20 μM	NI @ 1000	NI @ 250 μM
6a	2′,4′-Cl2	1200 ± 100c	50 ± 7 @ 10 μM	~1000	NI @ 250 μM
7a	2′,4′-Cl2	190 ± 30c	100 @ 2.5 μM	57 ± 10	NI @ 500 μMc
7e	2′-Cl,4′-Me	340 ± 50c	100 @ 2.5 μM	360 ± 40	NI @ 500 μMc
7i	2′-Cl,4′-F	506 ± 45	100 @ 2.5 μM	278 ± 27	21 ± 3 @ 250 μM
7j	2′-Cl,4′-Br	300 ± 40	100 @ 5 μM	21 ± 6	NI @ 250 μM
7k	2′-Br,4′-Cl	340 ± 60	100 @ 5 μM	31 ± 4	NI @ 250 μM
8a	2′,4′-Cl2	~5000	ND	~1000	NI @ 250 μM
9a	2′,4′-Cl2	>20 000	ND	~5% inh. @ 1000	NI @ 250 μM
10a	2′,4′-Cl2	>10 000	ND	ND	ND
11a	2′,4′-Cl2	10 000 ± 1600c	NI @ 20 μM	7% inh. @ 1000	45 ± 10 @ 250 μM

^aExcept for (±)-11a, all compounds are trans- and are (1R,3S)-configured.

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

^cData reported previously.¹³

^dDrug at indicated concentration.

^eRecombinant P. falciparum IspD IC₅₀ values measured at 60 nM Pf IspD.

^fPercent growth inhibition at the indicated concentration. NI signifies “no inhibition”; ND signifies “not determined”. Values represent averages of at least two independent assays ± SEM.