Table 1. Biochemical Activity of Tested Compounds against PvNMT and Human NMTs ^a.

					Kiapp (μM)
Cmpd	R2	R3	R4	R6	PvNMT	HsNMT1	HsNMT2	cLog Pc	LEd	LipEe
1	Me	nBu	S-(CH2)2-CN	MeO	1.73 ± 0.16	1.69 ± 0.22	11.39 ± 2.11	4.9	0.36	0.9
5b	Me	Et	S-(CH2)2-CN	MeO	3.23 ± 0.19	15.63 ± 1.37	23.23 ± 2.53	3.9	0.37	1.6
6	Me	H	S-(CH2)2-CN	MeO	> 100	> 100	> 100	2.5
7	H	CO2E	S-(CH2)2-CN	MeO	4.74 ± 0.24	19.43 ± 0.86	>100	3.0	0.33	2.4
		t
8	H	CO2E	S-(CH2)2-CN	H	24.42 ± 1.79	> 100	> 100	2.7	0.31	1.9
		t
9	Me	CO2E	S-(CH2)2-CN	H	24.37 ± 0.53	10.80 ± 0.91	41.53 ± 6.23	3.2	0.30	1.4
		t
10	Et	CO2E	S-(CH2)2-CN	H	60.63 ± 4.72	47.92 ± 7.84	94.17 ± 6.23	3.8	0.26	0.5
		t
11	nPr	CO2E	S-(CH2)2-CN	H	> 100	> 100	> 100	4.3
		t
12	Me	nBu	s-(ch2)2-c=ch	MeO	11.60 ± 1.39	> 100	> 100	5.4	0.31	−0.5
13	Me	nBu	S-(CH2)3-CN	MeO	35.23 ± 7.64	47.60 ± 3.51	46.06 ± 13.04	5.3	0.26	−0.8
14	Me	nBu	S-CH2-CN	MeO	> 100			4.6
15	Me	nBu	S-(CH2)3-OH	MeO	17.35 ± 0.84	> 100	> 100	5.0	0.30	−0.2
16	Me	nBu	S-(CH2)2-Ph	MeO	> 100			6.7
17	Me	CO2E	NH-(CH2)-CN	H	>100			3.7
		t
18b	Me	nBu	S-(CH2)2-CN	H	2.46 ± 0.16	> 100	> 100	4.6	0.38	1.0
19b	Me	nBu	S-(CH2)2-CN	Br	21.55 ± 2.38	> 100	> 100	5.5	0.30	−0.9
20	H	CO2E	S-(CH2)2-CN	F	7.77 ± 0.38	33.48 ± 9.61	37.52 ± 10.69	2.9	0.33	2.2
		t
21	H	CO2E	S-(CH2)2-CN	Me	6.97 ± 0.54	27.49 ± 2.40	> 100	3.2	0.33	1.9
		t
22	H	CO2E	S-(CH2)2-CN	Cl	10.39 ± 0.80	> 100	> 100	3.5	0.32	1.5
		t
23	H	CO2E	S-(CH2)2-CN	Acetyl	> 100			2.0
		t
24	H	CO2E	S-(CH2)2-CN	CH3-CH(OH)	> 100			2.8
		t

^aApparent K_i values of tested compounds on the enzymatic activity of recombinant P. vivax NMT and Homo sapiens NMT isoforms 1 and 2. Each K_i is the mean ± SD from duplicates.

^bPurchased compound from Interbioscreen Ltd. Purity > 85% based on RP-HPLC/MS analysis.

^ccLog P values were calculated with ChemDraw for Excel version 12.0.2.

^dLE: ligand efficiency (PvNMT); LE = −RTln(K_i^app)/N where N is the number of non-hydrogen atoms of the compound.

^eLipE: lipophilic efficiency (PvNMT); LipE = pIC₅₀ - cLog P.