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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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%
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
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))
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