Table 2.

EC₅₀ and IC₅₀ values for the six selected compounds in various yeast, parasite, red blood cell, and physicochemical assays.^a

	Compounds
	GSK-1	GSK-2	GSK-3	GSK-4	GSK-5	GSK-6
Yeast HTS Growth Assay-GSK (μM)	3.16	0.25	2.51	3.98	63.1	10
Yeast Kill Assay-GSK (μM)	0.63	<0.08	0.63	1.26	6.31	1.26
Yeast Kill Assay-Akabas lab (μM)	0.54 ± 0.20	0.11 ± 0.04	0.46 ± 0.30	0.43 ± 0.30	4.0 ± 1.3	1.2 ± 1.1
PfENT1 [3H]Ado uptake (μM)	0.12 ± 0.08	0.03 ± 0.03	0.03 ± 0.01	0.02 ± 0.01	2.59 ± 2.36	3.98 ± 1.35
PvENT1 [3H]Ado uptake (μM)b	0.14 ± 0.07	0.04 ± 0.03	0.04 ± 0.01	0.02 ± 0.04	2.71 ± 0.25	NEd
PbENT1 [3H]Ado uptake (μM)c	0.13 ± 0.05	0.05 ± 0.03	0.07 ± 0.04	0.01 ± 0.01	3.09 ± 2.70	NEd
3D7 (μM)	0.78 ± 0.2	2.25 ± 0.4	2.38 ± 0.5	6.20 ± 1.9	8.72 ± 1.6	10.3 ± 4.7
PfENT1-KO (μM)	17 ± 4.8	2.66	Low activity/NEe	29.4 ± 0.5	10.8	NEe
Dd2 (μM)	0.11 ± 0.009	1.89 ± 0.2	0.59 ± 0.05	1.90 ± 0.4	10.6 ± 2.1	3.3 ± 1.7
HB3 (μM)	0.34 ± 0.1	3.55 ± 0.7	2.21 ± 0.6	6.16 ± 2.5	9.09 ± 4.5	19.7 ± 4.1
7G8 (μM)	0.48 ± 0.2	4.52 ± 0.1	6.08 ± 1.3	8.44 ± 2.4	16.1 ± 5.5	19.0 ± 3.5
Cam3.II Artemisinin resistant (μM)	0.16 ± 0.09	1.37 ± 0.2	0.79 ± 0.2	3.02 ± 1.6	8.37 ± 1.4	6.07 ± 1.0
hENT1 [3H]adenosine uptake into RBC (μM)	0.99 ± 0.81	24.5 ± 24.8	72.4 ± 19.3	51.0 ± 27.7	Low activity/NEd	NEd
hFNT [3H]hypoxanthine uptake into RBC (μM)	0.38 ± 0.1	NEd	9.93 ± 4.1	NEd	3.54 ± 1.5	NEd
HepG2 cell cytotoxicity (μM)f	>100	>100	>100	>100	>100	>100
Molecular weight	475	402	363	341	254	338
Solubility (μg/mL)	10.5	2.5	112	156	16	>133
ChromLogDpH7.4g	4.8	6.8	4	4.5	3.7	1.2
PFIh	8.8	9.6	6	6.5	5.7	4.2
HSA Column bindingi	94%	97%	84%	92%	90%	48%

^aValues are mean ± SD. N ≥ 3 for all experiments except for the “5-FUrd growth assay-GSK” and the “Ado dependent growth-GSK columns”, where N=2, and for the PfENT1-KO experiments with compounds GSK-2 and GSK-5, where N=1.

^bPvENT1, yeast expressing the P. vivax ENT1 homologue

^cPbENT1, yeast expressing the mouse malaria model P. berghei ENT1 homologue

^dNE, no effect at the maximum concentration tested, 100 μM. Low activity/NE, indicates that at the highest concentration tested there seemed to be an effect, but it was not sufficient to calculate an IC₅₀ value.

^eNE, no effect at the maximum concentration tested, 74.2 μM. Low activity/NE, indicates that at the highest concentration tested there seemed to be an effect, but it was not sufficient to calculate an IC₅₀ value.

^fFor the HepG2 cell cytotoxicity data, and >100 indicates no cytotoxicity up to 100 μM.

^gChromLogD_pH7.4, chromatographic log of the distribution constant at pH 7.4.^{59, 60, 63}

^hPFI, Property Forecast Index.^{31, 63}

ⁱHSA, human serum albumin.⁶¹