Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum

Malaria Journal

Table 2 Summary of compounds with their identification number, main physicochemical properties and bioactivities

Compound	MW (g/mol)	xLogP^a)	tPSA NOPS^a)	EC₅₀in nM^b)(3D7)	EC₅₀in nM^c)(NF54)	pEC₅₀^d)(3D7)	pEC₅₀^d)(NF54)	LEI^e)(3D7)	LEI^e)(NF54)	Comment
1	276.53	4.1	49	602	4700	6.2	5.3	22.5	19.2	Weakly active/unstable
2	504.62	9.5	57	ND	763	N/A	6.1	N/A	12.1	-
3	434.57	4.2	99	222	3000	6.7	5.5	15.3	12.7	Weakly active
4	281.81	2.9	58	172	ND	6.8	N/A	24.0	N/A	-
4a	281.81	2.9	58	ND	>10000	N/A	<5	N/A	<17.7	Inactive
5	399.44	5.0	65	870	3898	6.1	5.4	15.2	13.5	Weakly active
6	299.37	2.7	50	<10	>10000	>8.0	<5.0	>26.7	<16.7	Inactive
7	337.38	4.3	89	648	450	6.2	6.3	18.3	18.8	Validated hit, CHEMBL587310^f)
8	344.43	3.3	119	297	284	6.5	6.5	19.0	19.0	Validated hit
9	432.39	4.9	70	393	309	6.4	6.5	14.8	15.1	Validated hit
10	516.28	4.4	96	181	60	6.7	7.2	13.0	14.0	Validated hit
11	396.47	5.4	61	433	518	6.4	6.3	16.1	15.9	Validated hit
12	368.39	4.9	68	928	60	6.0	7.2	16.4	19.6	Validated hit, CHEMBL1545915^f)
13	265.38	4.4	120	194	102	6.7	7.0	25.3	26.3	Validated hit
14	361.22	4.3	65	350	ND	6.5	N/A	18.0	N/A	CHEMBL527593^f)
14a	361.22	4.3	65	ND	>10000	N/A	<5	N/A	<13.8	Inactive
14b	361.22	4.3	65	ND	167	N/A	6.8	N/A	19.7	Hit
14c	361.22	4.3	65	ND	4200	N/A	5.4	N/A	14.9	Weakly active
14d	361.22	4.3	65	ND	>10000	N/A	<5	N/A	<13.8	Inactive
15	441.59	3.4	78	678	ND	6.7	N/A	14.0	N/A	-
15a	441.59	3.4	78	ND	44	N/A	7.4	N/A	16.7	Hit
15b	441.59	3.4	78	ND	679	N/A	6.2	N/A	14.0	Hit
15c	413.53	2.4	78	ND	535	N/A	6.3	N/A	15.2	Hit
16	414.54	5.3	59	990	ND	6.0	ND	12.1	N/A	-
17	431.96	6.2	36	ND	309	ND	6.5	N/A	15.1	Hit

ND: not determined; N/A: not applicable; ^a)calculated with the Dotmatics Vortex software; ^b)EC₅₀ determined with the P. falciparum 3D7 strain with DAPI imaging (HTS screen) see experimental; ^c)EC₅₀ determined with the P. falciparum NF54 strain by ³Hypoxanthine incorporation (Hit validation) see experimental; ^d)half maximal effective concentration (EC₅₀) expressed as a negative logarithm of the molar concentration; ^e)Ligand Efficiency Index (LEI) = pEC₅₀/(MW/1000); ^f)CHEMBL_ID upon successful search in ChEMBL Malaria. NB: 12 (MMV396749) and 14 (MMV008138) were placed in the public domain in July 2011.

ISSN: 1475-2875