Table 3.

Summary of Series III compounds: antimalarial activity on CQ-resistant strain K1 and CQ-sensitive strain 3D7, solubility, and permeability across an artificial membrane (PAMPA)

	Aryl group	EC50 (μM)a K1 strain	EC50 (μM)a 3D7 strain	Solubility (μM)b	Permeability (10−6 cm/s)c
7	m,p-methylenedioxy-phenyl	0.25±0.01	0.24±0.02	>100	100±13
31a	phenyl	0.82±0.07	0.79±0.04	>100	194±41
31b	2-thienyl	3.10±0.60	2.87±0.01	>100	105±10
31c	m-MeO-phenyl	0.13±0.01	0.10±0.01	>100	172±19
31d	m-Me-phenyl	0.30±0.01	0.29±0.01	48±8	227±7
31e	m-CF3-phenyl	0.22±0.02	0.21±0.02	19±1	569±80
31f	m-Cl-phenyl	0.18±0.02	0.20±0.01	58±8	948±39
31g	m-F-phenyl	0.55±0.02	0.59±0.05	>100	188±14
31h	m-NO2-phenyl	0.87±0.01	0.84±0.02	13±1	397±19
31i	p-MeO-phenyl	1.15±0.22	1.35±0.12	8±2	196±20
31j	p-tBu-phenyl	1.02±0.03	1.93±1.69	2±0	876±54
31k	p-CF3-phenyl	>10	3.60±0.07	8±0	312±15
31l	p-Cl-phenyl	>10	2.09±0.27	3±0	501±71
31m	m,p-diCl-phenyl	2.90±2.80	2.52±0.90	17±3	763±19
31n	o-Me-phenyl	>10	>10	>100	100±13
31o	o-Cl-phenyl	>10	>10	28±1	674±81

^aEC₅₀ values are reported as the mean ± SD of at least two independent experiments. Positive controls were mefloquine (EC₅₀ in K1: 0.04±0.02 μM; EC₅₀ in 3D7: 0.16±0.02 μM) and chloroquine (EC₅₀ in K1: 1.61±0.30 μM; EC₅₀ in 3D7: 0.09±0.02 μM)

^bSolubility in PBS buffer, pH 7.4, containing 5% DMSO. The detection limit of the solubility assay was 100 μM. Two standards were tested in the same assay: albendazole (3±0.1 μM, poorly soluble) and carbamazepine (>100 μM, highly soluble).

^cPermeability at pH 7.4. Three standards were tested in the same assay: ranitidine HCl (1.2±0.7×10⁻⁶ cm/s, poorly permeable), carbamazepine (145±13×10⁻⁶ cm/s, moderately permeable), and verapamil HCl (1960±290×10⁻⁶ cm/s, highly permeable).