Table 3. Biological activities of inhibitors guided by overlaying crystal structures.

Compd no.	R2	R3	clog P a	PfNMT K i (μM)	LipE b	HsNMT K i (μM)	S.I. c	EC50 d (μM)	LD50 e (μM)
19		H	2.79	0.027	4.78	0.27	10	3.5	70
25		H	1.69	0.028	5.86	0.20	7	3.7	>100
26		Me	2.09	0.57	4.15	0.51	0.9	>30	n.d. f
27		Et	2.44	0.34	4.03	0.27	0.8	>10	n.d.
28		i-Pr	2.85	0.090	4.20	0.18	2	3.2	>100
30		H	3.14	0.0017	5.63	0.024	14	0.21	65

^aclog P values calculated using ChemAxon software.

^bLipE = pK _i (PfNMT) – clog P.

^cS.I., calculated as K _i(HsNMT1)/K _i(PfNMT).

^d P. falciparum, 3D7 line was used.

^eHepG2 cell line was used.

^fn.d. = not determined.