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Table 1 Cluster and activity of 32 compounds against Plasmodium falciparum NF54 gametocytes, asexual parasites and cytotoxicity of these compounds against HepG2

From: Novel lead structures with both Plasmodium falciparum gametocytocidal and asexual blood stage activity identified from high throughput compound screening

Cluster

Sample ID

Structure

Gametocyte, IC50 (µM)

Asexual, IC50 (µM)

HepG2, IC50 (µM)

Asexual/Gametocyte

Cluster 1

2,4-diaminopyrimidines

NCGC00134128

1.18 ± 0.17

1.93 ± 0.13

–

1.64

 

NCGC00134154

1.19 ± 0.34

2.83 ± 0.31

–

2.38

 

NCGC00134126

1.19 ± 0.05

4.78 ± 0.43

–

4.02

 

NCGC00134130

1.42 ± 0.24

3.26 ± 0.50

–

2.30

 

NCGC00134124

1.55 ± 0.11

5.96 ± 0.70

–

3.85

 

NCGC00134158

2.08 ± 0.18

4.70 ± 0.52

–

2.26

 

NCGC00134156

2.10 ± 0.73

3.53 ± 0.27

–

1.68

 

NCGC00134132

1.29 ± 0.32

2.41 ± 0.32

–

1.87

 

NCGC00134136

2.57 ± 0.48

4.12 ± 0.10

–

1.60

 

NCGC00134134

1.10 ± 0.16

3.12 ± 0.87

–

2.84

Cluster 2

3-amino-imidazo[1,2-a]pyridines

NCGC00104490

1.29 ± 0.29

2.22 ± 0.35

–

1.72

 

NCGC00106055

3.98 ± 1.12

4.18 ± 0.68

–

1.05

 

NCGC00106087

3.34 ± 0.51

7.49 ± 4.11

–

2.24

 

NCGC00106780

1.82 ± 0.11

3.53 ± 1.21

–

1.94

 

NCGC00106091

2.45 ± 0.42

4.51 ± 1.29

–

1.84

 

NCGC00106119

2.82 ± 0.30

4.22 ± 0.29

–

1.50

 

NCGC00104528

8.91 ± 0.20

13.9 ± 0.93

–

1.56

Cluster 3

4H-chromen-4-ones

NCGC00100599

4.34 ± 0.60

0.34 ± 0.03

–

0.08

 

NCGC00101506

4.82 ± 0.21

0.54 ± 0.05

–

0.11

 

NCGC00141020

4.86 ± 0.03

1.07 ± 0.37

–

0.22

 

NCGC00100597

6.04 ± 1.90

0.63 ± 0.05

–

0.10

Cluster 4

4-1H-pyrazol-5-yl piperidines

NCGC00127017

11.9 ± 2.05

3.44 ± 0.24

25.3 ± 5.41

0.29

 

NCGC00126892

31.3 ± 12.8

7.49 ± 0.86

34.4 ± 5.36

0.24

 

NCGC00127015

20.3 ± 0.31

3.05 ± 0.27

38.4 ± 0.48

0.15

 

NCGC00126987

30.6 ± 1.95

1.47 ± 0.04

38.6 ± 0.42

0.05

 

NCGC00124960

~60

35.6 ± 1.77

–

0.59

Cluster 5

8-quinolinol

NCGC00114940a

0.62 ± 0.04

1.16 ± 0.57

–

1.87

Cluster 6

3H-imidazo[4,5-b]pyridine

NCGC00134795

4.25 ± 0.64

0.96 ± 0.30

–

0.23

Cluster 7

thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine

NCGC00123034

35.2 ± 4.52

32.1 ± 12.6

–

0.92

Cluster 8

1 2 3 4-tetrahydroacridine

NCGC00110901

10.6 ± 1.32

36.1 ± 15.2

–

3.41

Cluster 9

thieno[2,3-d]pyrimidine

NCGC00104044

38.7 ± 57.9

9.94 ± 0.93

–

0.26

Cluster 10

10,11-dihydrodibenzo[b,f][1,4]thiazepine

NCGC00140326

~60

13.8 ± 0.82

–

0.23

  1. IC50, mean half-maximum inhibitory concentrations determined from experiments against P. falciparum NF54 gametocyte, asexual parasite and HepG2
  2. – Indicates compounds with less than 25% cytotoxicity at up to 46 µM
  3. a In HepG2 cytotoxicity assays, NCGC00114940 showed 35.7% response at 15.3 µM and 33.3% response at 46 µM. Data are presented as mean ± SD with n = 3