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34
APPENDIXES Supplementary Table 1. IC 50 determination in OCA for HEK 293 and P. yoelii cells. Number of independent experiments performed, structure, cluster numbers and P. falciparum whole cell data (Gamo et al., 2010) are also included. P. yoelii OCA HEK 293 OCA Compound Cluster (C) / Singleton (S)* Structure IC 50 (µM) n IC 50 (µM) n P. falciparum AWC XC 50 (µM)** TCMDC-138901 C-01 0.180 ± 0.070 2 >10 2 0.28 TCMDC-136197 C-01 0.155 ± 0.003 2 >10 2 0.33 N H H 3 C CH 3 Br O O N H O CH 3 O O F F F Br N H O H 3 C CH 3 Br O F

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Page 1: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

APPENDIXES

Supplementary Table 1. IC50 determination in OCA for HEK 293 and P. yoelii cells. Number of independent experiments performed, structure,

cluster numbers and P. falciparum whole cell data (Gamo et al., 2010) are also included.

                     P. yoelii OCA HEK 293 OCA

Compound Cluster (C) / Singleton (S)* Structure IC50 (µM) n IC50 (µM) n P. falciparum

AWC XC50 (µM)**

TCMDC-138901 C-01

 

0.180 ± 0.070 2 >10 2 0.28

NH

H3C CH3

Br

OO

NH

O

CH3

O

O

F

F

F

Br

NH

O

H3C CH3

Br

O

F

Page 2: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-136197 C-01   0.155 ± 0.003 2 >10 2 0.33

TCMDC-138928 C-01   0.181 ± 0.070  2 >10 2 0.08

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TCMDC-137416 C-01

 

0.209 ± 0.048 2 >10 2 0.21

H3C N CH3

Cl

OH

Cl

CH3

O

H3CHN

O

Cl

Cl

CH3NH3C

OH

Br

F

NH

O

H3C CH3

Cl

OCH3

NH

O

H3C CH3

F

F

F

O

O

F

F

F

Page 4: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-137267 C-01   0.564 ± 0.045 2 >10 2 0.84

TCMDC-137421 C-01   0.721 ± 0.227 2 >10 2 1.07

TCMDC-135655 C-01   0.290 ± 0.120 3 >10 2 0.07

TCMDC-135444 C-01   0.358 ± 0.165 3 >10 2 0.17

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TCMDC-135462 C-01

 

0.143 ± 0.113 3 >10 2 0.02

NH

O

H3C CH3

Cl F

F

NH

O

H3C CH3

Br

HN N

F

F

F

NH

O

H3C CH3

N

O

O

O

O

F

F

F

NH

O

Br

H3C CH3

F

F

NH

O

H3C CH3

Cl

OCH3

Page 6: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-135546 C-01   0.048 ± 0.008 3 >10 2 0.03

TCMDC-135555 C-01   0.834 ± 0.810 3 >10 2 0.25

TCMDC-135461 C-01   0.049 ± 0.012 3 >10 2 0.01

TCMDC-135654 C-01   0.149 ± 0.049 3 >10 2 0.02

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TCMDC-137377 C-01

 

0.229 ± 0.113  3 >10 2 0.11

2

CH3NH

NH3C

O O

Br

H3C N CH3

O

O

F FF

HCl

NH

O

Br

H3C CH3

ON

HCl

NH

O

Br

CH3

O

NH

O

H3C CH3

Br

F F

NH

O

H3C CH3

Cl

O

F

F

F

Page 8: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-135795 C-01   0.321 ± 0.108 3 >10 2 0.21

TCMDC-136196 C-01   0.253 ± 0.109 3 >10 2 0.68

TCMDC-134692 C-01   0.129 ± 0.035 3 >10 2 0.03

TCMDC-136060 C-01   0.137 ± 0.020 3 >10 2 0.04

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TCMDC-135303 C-01

 

0.258 ± 0.067 3 >10 2 0.41

NH

O

H3C CH3

Br

O

F

F

F

NH

O

H3C CH3

Cl

O CH3

NH

O

H3C CH3

OH3C

O

F F

F

NH

O

H3C CH3

Cl

O

OCH3

NH

O

Br

H3C CH3

O

F

F

F

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TCMDC-134729 C-01   0.333 ± 0.187 3 >10 2 0.20

TCMDC-135253 C-01   0.595 ± 0.163 3 >10 2 0.31

TCMDC-136134 C-01   0.154 ± 0.056 3 >10 2 0.14

TCMDC-134726 C-01   0.063 ± 0.016 3 >10 2 0.04

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TCMDC-134728 C-01

 

0.038 ± 0.023 3 >10 2 0.05

NH

O

H3C CH3

Cl

O

F

NH

O

H3C CH3

Br

OS

N

NH

O

H3C CH3

OS N

F

F

F

NH

O

Br

H3C CH3

O

O

F

F

F

CH3

O

H3C N

OH

O

F

FF

Page 12: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-135256 C-01   0.708 ± 0.289 3 >10 2 0.25

TCMDC-135289 C-01   0.454 ± 0.355 3 >10 2 0.53

TCMDC-138826 C-01   0.355 ± 0.076 3 >10 2 0.11

TCMDC-138136 C-01   0.213 ± 0.034 2 >10 2 0.60

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TCMDC-137266 C-01

 

0.450 ± 0.215 2 >10 2 0.20

CH3

O

H3CHN

OOF

FF

CH3

O

H3CHN

OCl

CH3NH3C

O

OH

Br

H3C N CH3

OH

Br

O

Cl

CH3NH3C

OH

I

O

O

F

FF

Page 14: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-137265 C-01   0.440 ± 0.314 2 >10 2 0.60

TCMDC-137419 C-01   0.425 ± 0.087 2 >10 2 0.78

TCMDC-137407 C-01   0.290 ± 0.066 2 >10 2 0.81

TCMDC-137387 C-01   0.198 ± 0.040 2 >10 2 0.13

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TCMDC-137325 C-01

 

0.521 ± 0.196 2 >10 2 0.56

CH3NH3C

O

OF

FF

OH

Br

CH3NH3C

OH

Br

O

Cl

2

CH 3

NH

N

H3C

O O

Cl

H3C N CH 3

O

O

FF

F

HCl

H3C N CH3

OH

Cl

S

O

O

Cl

CH3

OH

H3C N

S

Cl

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TCMDC-137420 C-01   0.610 ± 0.144 2 >10 2 0.59

TCMDC-137384 C-01   0.269 ± 0.034 2 >10 2 0.13

TCMDC-137412 C-01   0.375 ± 0.112 3 >10 2 0.14

TCMDC-137403 C-01   0.632 ± 0.089 3 >10 2 0.97

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TCMDC-133308 C-01

 

1.010 ± 0.063 3 >10 2 0.63

NH

O

H3C CH3

OF

FF

NH

O

Cl

H3C CH3

O

F

NH

O

H3C CH3

O

O

F

F

F

NH

O

Br

H3C CH3

OCH2

NH

O

H3C CH3

Br

OO

N

F

F

F

Page 18: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-132415 C-01   1.691 ± 0.746 3 >10 2 0.57

TCMDC-132123 C-01   0.710 ± 0.258 3 >10 2 0.74

TCMDC-135042 C-01   0.712 ± 0.360 3 >10 2 0.28

TCMDC-135554 C-01   0.101 ± 0.025 3 >10 2 0.14

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TCMDC-135678 C-01

 

0.450 ± 0.027 3 >10 2 0.10

NH

O

Cl

H3C CH3

NH2

NH

O

H3C CH3

N

O

O

O

NH

O

H3C CH3

Br

OS

N

2

NH3C CH3

Br

O

N

O

H3C

O

O

F

F

F

NH

CH3

HCl

2

NH3C CH3

Br

O

N

OO

O

F

F

F

CH3

H3CNH

CH3H3C

HCl

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TCMDC-135779 C-01   0.237 ± 0.063 3 >10 2 0.27

TCMDC-135220 C-01   0.964 ± 0.123 3 >10 2 0.39

TCMDC-132416 C-01   2.660 ± 0.457 3 >10 2 0.39

TCMDC-132417 C-01   1.398 ± 0.111 3 >10 2 0.17

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TCMDC-136051 C-02

 

0.271 ± 0.001 2 >10 2 0.09

NH

O

H3C CH3

Cl N

F

F

F

NH

O

H3C CH3

Br N

O

F

F

NH

O

Cl

H3C CH3

N

O

F

F

NH

O

H3C CH3

Br N

O

F

F

F

NH

O

Cl

H3C CH3

N F

F

F

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TCMDC-135683 C-02   0.313 ± 0.065 3 >10 2 0.10

TCMDC-135676 C-02   0.165 ± 0.055 3 >10 2 0.09

TCMDC-135656 C-02   0.086 ± 0.025 3 >10 2 0.04

TCMDC-136014 C-02   0.100 ± 0.029 3 >10 2 0.10

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TCMDC-135677 C-02

 

0.224 ± 0.025 3 >10 2 0.20

NH

O

Cl

H3C CH3

N

O

F

F

F

NH

O

H3C CH3

Br N

CH3

HCl

NH

O

Br

H3C CH3

N

FF

F

F

F

F

NH

O

Br

H3C CH3

N FF

F

NH

O

H3C CH3

N

O

FF

F

F

F

F

Cl

Page 24: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-135687 C-02   0.094 ± 0.008 3 >10 2 0.06

TCMDC-136015 C-02   0.092 ± 0.065 3 >10 2 0.08

TCMDC-135881 C-02   0.984 ± 0.576 3 >10 2 0.17

TCMDC-135814 C-02   0.168 ± 0.038 3 >10 2 0.11

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TCMDC-135796 C-02

 

0.046 ± 0.028 3 >10 2 0.02

NH

O

Br

H3C CH3

N

O

F

F

F

NH

H3C CH3

Br

O

N F

F

F

NH

O

H3C CH3

Br N

O

FF

F

F

F

F

NH

O

H3C CH3

Cl N H3C

NH

O

Br

H3C CH3

N

O

O

F

F

F

Page 26: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-135911 C-02   0.156 ± 0.063 3 >10 2 0.14

TCMDC-135815 C-02   0.105 ± 0.042 3 >10 2 0.15

TCMDC-135816 C-02   0.315 ± 0.149 3 >10 2 0.36

TCMDC-135254 C-02   0.174 ± 0.043 3 >10 2 0.14

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TCMDC-136303 C-02

 

0.240 ± 0.085 3 >10 2 0.22

NH

O

H3C CH3

Cl N Cl

NH

O

Br

H3C CH3

N F F

F

F

F

F

NH

O

Br

H3C CH3

N Cl

NH

O

H3C CH3

Cl N

O

F

F

F

NH

O

H3C CH3

Cl N

Cl

Page 28: ars.els-cdn.com · Web view0.113 ± 0.053 2 >10 2 0.61 TCMDC-125709 C-11 0.585 ± 0.147 2 >10 2 0.91 TCMDC-123689 C-11 8.192 ± 1.256 3 >10 2 1.35 TCMDC-125391

TCMDC-136013 C-02   0.116 ± 0.018 3 >10 2 0.19

TCMDC-136157 C-02   0.463 ± 0.139 3 >10 2 0.17

TCMDC-136286 C-02   0.191 ± 0.069 3 >10 2 0.07

TCMDC-136301 C-02   0.348 ± 0.164 3 >10 2 0.11

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TCMDC-135271 C-02

 

0.117 ± 0.022 3 >10 2 0.07

NH

O

H3C CH3

Cl N

O

O

F

F

F

H3C

H3C N CH3

NOH

H3C

H3C N CH3

Cl

OH

and1

and1

H3C N CH3

Cl

OH

Cl

N

O

CH3

O

O

O

CH3

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TCMDC-137431 C-03   0.099 ± 0.025 2 >10 2 0.40

TCMDC-137538 C-03   0.056 ± 0.017 2 >10 2 0.23

TCMDC-137423 C-03   0.042 ± 0.001 2 >10 2 0.05

TCMDC-141680 C-04   1.589 ± 0.912 3 >10 2 0.95

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TCMDC-124160 C-04

 

0.097 ± 0.014 2 >10 2 0.41

NN

O O

FO

CH3

CH3

NH

O

Cl

H3C

N

CH3

CH3

N

OH

H3C

N

O

F

F

F

NH

O

CH3

OF

FF

GW84130356-79%

GSK183490921-44%

NH

OF

CH3 Cl CH3NH

F

O

Cl

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TCMDC-136185 C-05   0.770 ± 0.589 3 >10 2 0.13

TCMDC-136129 C-05   0.274 ± 0.062 3 >10 2 0.02

TCMDC-137042 C-05   1.908 ± 0.264 3 >10 2 0.48

TCMDC-138812 C-06   0.816 ± 0.417 3 >10 2 0.23

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TCMDC-125226 C-06

 

0.341 ± 0.028 3 >10 2 0.38

NH

O

CH3

CH3

H3C

GW84130321-44%

GSK183490956-79%

NH

OF

CH3 Cl CH3NH

F

O

Cl

H3C

H3C

N

O

CH3

HO

CH3

CH3N

OH

CH3

CH3

HN

O

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TCMDC-138813 C-06   0436 ± 0.093 3 >10 2 0.35

TCMDC-138010 C-06   0.158 ± 0.019 2 >10 2 0.12

TCMDC-137425 C-06   0.195 ± 0.089 2 >10 2 0.21

TCMDC-137268 C-06   0.354 ± 0.018 2 >10 2 0.16

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TCMDC-137173 C-06

 

0.057 ± 0.001 2 >10 2 0.06

N

HO O

H3C

CH3H3C

and1

and1

H3CO

OH

Cl

CH3N

N

OH

CH3

CH3

Cl

CH3

NH

O

NH

O

Br

CH3

H3C

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TCMDC-137422 C-06   0.400 ± 0.033 3 >10 2 0.65

TCMDC-124085 C-06   0.554 ± 0.208 3 >10 2 0.20

TCMDC-123947 C-07   1.099 ± 0.232 2 >10 2 0.86

TCMDC-124347 C-07   2.236 ± 0.355 3 >10 2 0.81

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TCMDC-135219 C-07

 

0.860 ± 0.761 3 >10 2 0.64

NH

O

Br

H3C

N

H3C

O

NH

CH3NH

O

CH3

N

NH

O

OH3C

H3C

HN

S O

O

HO O

F

FF

SHN

N

O

O

N

NH

O

O

OCH 3

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TCMDC-132026 C-08   0.512 ± 0.038 2 >10 2 0.32

TCMDC-137186 C-08   0.159 ± 0.011 3 >10 2 0.51

TCMDC-134575 C-09   0.514 ± 0.225 3 >10 2 0.57

TCMDC-124874 C-09   0.760 ± 0.109 3 >10 2 0.70

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TCMDC-124699 C-10

 

0.280 ± 0.171 2 >10 2 0.50

N

NNH

O

NS

O

O

O

Br

NN

HN

ON

SO

O

OCl

S

S

N O

O

N

N

HN

S

O

Cl

N

N

HN

N

SO

O

O

CH 3

HNO

HO

O OH

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TCMDC-124698 C-10   0.411 ± 0.123 2 >10 2 0.36

TCMDC-124701 C-10   1.141 ± 0.439 3 >10 2 0.87

TCMDC-125243 C-10   0.710 ± 0.231 3 >10 2 0.08

TCMDC-125868 C-11   0.141 ± 0.007 2 >10 2 0.70

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TCMDC-123758 C-11

 

0.283 ± 0.154 3 >10 2 0.29

NH

O O

OH S

CH3

NH

O O

OHCH3

O

NH

O

O

O

O

O

CH3

CH3

HN

OS

O

O

Cl

HO

NH

O O

NOH

CH3

CH3

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TCMDC-123479 C-11   0.113 ± 0.053 2 >10 2 0.61

TCMDC-125709 C-11   0.585 ± 0.147 2 >10 2 0.91

TCMDC-123689 C-11   8.192 ± 1.256 3 >10 2 1.35

TCMDC-125391 C-11   0.205 ± 0.058 3 >10 2 0.23

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TCMDC-125470 C-11

 

0.558 ± 0.083 3 >10 2 0.34

N

O

N O

N

OH

HN

SN

O

H3C

CH3

N

SHN

OO

OCH3 CH3

N

O

ClS

O

HN

N

HO O

F

FF

N

O

Cl

S

O

HN

F

HO O

F

FF

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TCMDC-124428 C-12   1.846 ± 0.561 3 >10 2 0.56

TCMDC-124486 C-12   0.232 ± 0.066 3 >10 2 0.30

TCMDC-133955 C-13   2.430 ± 0.374 2 >10 2 0.58

TCMDC-133757 C-13   2.181 ± 1.608 3 >10 2 0.13

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TCMDC-133970 C-13

 

2.615 ± 0.996 3 >10 2 0.39

N

O

Cl

S

O

NH

HO O

F

FF

NN

N

O

HO

H3C

CH3

NN

N

OH

H3C

H3C

CH3N

OHCl

N

HN

N

CH 3

H3C

CH 3

O

HO O

F

FF

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TCMDC-125325 C-14   3.368 ± 1.365 3 >10 2 0.82

TCMDC-124479 C-14   0.247 ± 0.026 3 >10 2 0.22

TCMDC-137172 S-01   0.748 ± 0.030 2 >10 2 1.00

TCMDC-133823 S-02   2.201 ± 1.951 3 >10 2 0.52

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TCMDC-125039 S-03

 

1.096 ± 0.131 2 >10 2 1.16

NN

HN

ON

N

O

H3 C

CH 3

NH

N

N

NH

HN

N

O

CH3

Cl

OH

O

HCl

N

O

O

O

O

H3C

CH3

NN

N

NN

O

NH2

NH2

CH3 CH3

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TCMDC-124578 S-04   0.292 ± 0.249  3 7.521 ± 3.840 2 0.60

TCMDC-138029 S-05   0.974 ± 0.294 3 >10 2 0.30

TCMDC-124577 S-06   0.028 ± 0.010 3 >10 2 0.06

TCMDC-125024 S-07   0.257 ± 0.000 2 >10 2 0.07

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TCMDC-134937 S-08

 

1.319 ± 0.835 3 >10 2 0.58

N

Cl

NH

N

N

N

N

O

Cl

H3C

O

O

F

F

F

Na

N

OH

Cl

H3C

O

O

F

F

F

N

S

OH

O

O

CH3

N

O

OH

OCH3

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TCMDC-136021 S-09   0.116 ± 0.054 3 >10 2 0.04

TCMDC-136022 S-10   0.520 ± 0.180 3 >10 2 0.04

TCMDC-131540 S-11   0.102 ± 0.021 2 >10 2 0.37

TCMDC-125724 S-12   0.185 ± 0.002 2 >10 2 0.24

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TCMDC-134513 S-13

 

0.638 ± 0.010 2 >10 2 0.22

NH

O

N

CH3

CH3

O

OCH3

CH3

H3C

HN

NH

F F

F

NH3 C

S

O O

HN

HO O

F

FF

CH3

CH3

N

N

N

H2N N NH2

N

Cl

Cl

3N

NH

N

H3CN N

HO O

F

FF

N

HO

O

O

H3C

H3C

N

CH3

CH3

HO

O

OH

O

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TCMDC-133087     > 20 3 >10 2 0.85

TCMDC-137675     > 20 2 >10 2 0.16

TCMDC-133916     > 20 2 >10 2 0.13

TCMDC-131499     > 20 2 >10 2 0.36

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TCMDC-131493  

 

> 20 2 >10 2 0.18

OH

NH

Cl

CH3

S

H3CHBr

3N NH

NN

N

HO O

F

FF

N

N

NH

NH

CH3

NH

CH 3

HO

N

N

O

Cl

Cl

HN

ONH

N

HO O

F

FF

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TCMDC-132921     > 20 3 >10 2 0.15

TCMDC-133459     > 20 3 >10 2 0.99

TCMDC-140065     > 20 3 >10 2 1.09

TCMDC-136633     > 20 3 >10 2 0.73

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TCMDC-132758  

 

> 20 3 >10 2 0.84

HN

NH

N

CH3

N

O

HO O

F

FF

N

NH

N

F

FF

N

N NHO O

F

FF

and1

and1

HN

N

NH

O OCH3

OCH3

N

HNO

O

F

FF

CH3H2C

N

NH

H3C

H3C

NH

NH

NH

N

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TCMDC-133113     > 20 3 >10 2 0.96

TCMDC-139893     > 20 2 >10 2 0.65

TCMDC-139030     > 20 2 >10 2 0.70

TCMDC-140069     > 20 2 >10 2 0.77

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TCMDC-140513  

 

> 20 2 >10 2 0.77

NH

N S

NH

O

H3C

H3C

N

and1

and1

HN

N

NH

O

HN

F

NH

O

O

2

3NH

N

HO

OH H

and1

and1

O

H3C

CH3

CH3

CH3

OH

NH

ON

HN

N

HNN

O

CH3

Cl

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TCMDC-139889     > 20 2 >10 2 0.80

TCMDC-131498   > 20 2 >10 2 0.86

TCMDC-139890     > 20 2 >10 2 0.88

TCMDC-142105     > 20 2 >10 2 0.87

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TCMDC-142107  

 

> 20 2 >10 2 0.93

N

HN

O

N

H3C

F

N

HNN

Cl

S

and1

and1

NNH

ON

HN

NH

O

CH3

O

O

OH

CH3

CH3

O

O

CH3

CH3

GSK1203537 = Possible isomer

and1and1

HN

O

NH

HN

N

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TCMDC-123969     > 20 2 >10 2 0.92

TCMDC-139888     > 20 2 >10 2 1.13

TCMDC-125636     > 20 3 >10 2 0.78

TCMDC-133253     > 20 3 >10 2 1.07

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TCMDC-133351  

N

N

S OO

NH 2

CH 3

O

CH 3

 

> 20 3 >10 2 0.19

* Compounds with IC50 > 20 mM in P. yoelii OCA were not assigned to clusters

** P. falciparum Whole Cell Time Extended 72 hours (Gamo et al., 2010)

Supplementary Table 2. Data for speed of killing of some of the compounds tested in the screening and their activity in OCA in P. yoelii.

MMV Code* TCMDC Code Viability assay* % Inhibition in P. yoelii OCA at 2 µMMMV665939 TCMDC-123789 Slow 1%MMV019066 TCMDC-123587 Slow 2%MMV019662 TCMDC-124312 Slow 23%MMV007564 TCMDC-124400 Fast/moderate 46%MMV020750 TCMDC-125505 Moderate 0%MMV665928 TCMDC-123502 Fast 4%MMV006767 TCMDC-123992 Moderate 20%MMV019017 TCMDC-123535 Fast 10%MMV009063 TCMDC-124168 Fast 0%MMV665794 TCMDC-124162 Moderate 17%MMV006455 TCMDC-125708 Fast 20%MMV665888 TCMDC-125220 Moderate 4%Atovaquone Slow 100%Chloroquine Fast 0%

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Mefloquine TCMDC-123920 Fast 23%

*According to Linares et al., 2015

Supplementary Table 3. Statistics of TCAMs screening for IC50 determination of OCA in HEK 293 and P. yoelii cells.

P. yoeliiPlate code JXF JXW JY1 JXM JXD JX4 JXL JXQ JXI JXR JXH JXP

AVG C1 1.11 2.08 1.53 2.60 1.63 1.74 1.66 1.91 0.90 1.34 2.10 1.57

SD C1 0.16 0.21 0.30 0.29 0.17 0.30 0.28 0.19 0.12 0.17 0.31 0.18

AVG C2 -0.11 -0.15 -0.10 -0.15 -0.12 -0.11 -0.10 -0.07 -0.09 -0.08 -0.12 -0.11

SD  C2 0.01 0.02 0.01 0.01 0.01 0.01 0.01 0.04 0.01 0.01 0.02 0.01

% CV 14.48 10.33 19.83 11.32 10.27 17.16 17.04 9.70 13.89 12.59 14.63 11.33

S/B 10.26 13.54 14.95 17.40 13.75 15.18 17.43 25.97 9.81 17.10 17.34 14.50

Z' 0.58 0.69 0.42 0.66 0.70 0.50 0.50 0.65 0.60 0.63 0.56 0.67

Valid Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

HEK 293Plate code JXU JXF JXX JXJ IXK JXG JX3 JXC JXS JQ4 JPP JXN JXH JXT

AVG C1 2.23 1.11 2.37 2.64 1.73 1.88 1.33 1.70 1.07 3.63 4.26 7.60 5.98 1.05

SD C1 0.30 0.16 0.25 0.18 0.19 0.28 0.29 0.48 0.26 0.87 0.78 0.80 0.75 0.42AVGC2 0.07 -0.11 0.06 -0.23 -0.17 -0.16 -0.12 -0.17 -0.15 -0.14 -0.12 -0.11 -0.06 -0.15

SD C2 0.09 0.01 0.08 0.02 0.02 0.02 0.01 0.02 0.02 0.02 0.03 0.03 0.05 0.01

% CV 13.2 14.48 10.43 6.91 11.27 14.62 22.11 27.91 23.92 24.01 18.32 10.49 12.54 39.83

S/B 29.7 10.26 42.29 11.69 10.33 11.80 10.62 10.03 7.09 25.92 35.60 68.41 97.59 7.05

Z' 0.46 0.58 0.57 0.79 0.66 0.56 0.37 0.21 0.32 0.29 0.45 0.68 0.60 -0.08

Valid Yes Yes Yes Yes Yes Yes No No No No Yes Yes Yes No

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C1, Control 1 Positive untreated controlC2, Control 2 Negative control, stigmatellin 10 µMAVG AverageSD Standard Deviation% CV Coefficient of variation (CV= (SD Control 1/AVG Control 1)*100)S/B AVG Control 1 / AVG Control 2Z' Z' = (1-3*ABS((SD Control 1 + SD Control 2 / (AVG Control 1 - AVG Control 2))

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Supplementary Table 4. Proportion of mature forms in P. falciparum preparations used in this work and corresponding Vmax for oxygen

consumption.

Total parasitemia (%) Mature form parasitemia(%)

Vmax untreated control( RFUs/s)

Preparation 1 13.6 9.6 0.24Preparation 2 13.0 11.2 0.28Preparation 3 11.0 7.5 0.28Preparation 4 11.8 10.2 0.26Preparation 5 15.0 12.5 0.16Preparation 6 11.0 9.2 0.11Preparation 7 12.0 9.4 0.14Preparation 8 11.5 11.1 0.15Preparation 9 13.3 11.3 0.12Preparation 10 13.0 12.0 0.17Preparation 11 11.8 9.4 0.10