Antimalarials Active against the Five Gametocyte Stages |
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Plouffe DM, Wree M, Du AY, Meister S, Li F, Patra K, Lubar A, Okitsu SL,Flannery EL, Kato N, Tanaseichuk O, Comer E, Zhou B, Kuhen K, Zhou Y, Leroy D,Discovery of Small Molecules that Interrupt Malaria Transmission. Cell Host Microbe. 2016 Jan 13;19(1):114-26. doi: 10.1016/j.chom.2015.12.001. Epub 2015 Dec 31. PMID: 26749441 |
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Antimalarials Active against Asexual Blood Stages Tested against the Five Gametocyte Stages |
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Compound |
Chemical Class |
EC50 (μM) ± STD |
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Oocyst Reduction |
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Stage I |
Stage II |
Stage III |
Stage IV |
Stage V |
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Artemisinin |
Endoperoxide |
0.024 ± 0.001 |
0.020 ± 0.010 |
0.012 ± 0.002 |
0.037 ± 0.003 |
>12.500 ± 0.000 |
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Artemisone |
Endoperoxide |
0.003 ± 0.000 |
0.002 ± 0.000 |
0.003 ± 0.000 |
0.004 ± 0.001 |
>12.500 ± 0.000 |
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Artemether |
Endoperoxide |
0.016 ± 0.006 |
0.005 ± 0.001 |
0.006 ± 0.002 |
0.019 ± 0.004 |
>12.500 ± 0.000 |
10 μM: 75%–99%3 |
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Artenimol (Dihydroartemisinin) |
Endoperoxide |
0.006 ± 0.001 |
0.003 ± 0.001 |
0.007 ± 0.000 |
0.021 ± 0.008 |
>12.500 ± 0.000 |
1 μM: ∼90%1 |
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Artesunate |
Endoperoxide |
0.008 ± 0.002 |
0.004 ± 0.000 |
0.013 ± 0.003 |
0.049 ± 0.013 |
>10.601 ± 2.686 |
1 μM: ∼55%1 |
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OZ439 mesylate |
Endoperoxide |
0.011 ± 0.001 |
0.005 ± 0.000 |
0.003 ± 0.000 |
0.002 ± 0.000 |
>12.500 ± 0.000 |
1 μM: 100%1 |
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OZ277(RBX-11160) |
Endoperoxide |
0.008 ± 0.001 |
0.004 ± 0.000 |
0.002 ± 0.000 |
0.008 ± 0.003 |
>12.500 ± 0.000 |
10 μM: 75%–99%3 |
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Amodiaquine |
4-aminoquinoline |
0.012 ± 0.001 |
0.006 ± 0.001 |
0.096 ± 0.013 |
2.456 ± 0.757 |
1.783 ± 0.119 |
10 μM: 50%–74%3 |
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AQ-13 |
4-aminoquinoline |
0.043 ± 0.002 |
0.033 ± 0.000 |
0.484 ± 0.159 |
6.471 ± 0.888 |
6.051 ± 1.091 |
10 μM: 25%–49%3 |
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Chloroquine |
4-aminoquinoline |
0.096 ± 0.007 |
0.098 ± 0.005 |
>6.250 ± 0.000 |
>6.250 ± 0.000 |
>6.25 ± 0.000 |
10 μM: 25%–49%3 |
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Hydroxychloroquine |
4-aminoquinoline |
0.107 ± 0.011 |
0.131 ± 0.005 |
>4.489 ± 2.490 |
>6.250 ± 0.000 |
>6.25 ± 0.000 |
10 μM: 25%–49%3 |
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Naphthoquine |
4-aminoquinoline |
0.025 ± 0.003 |
0.014 ± 0.000 |
0.296 ± 0.078 |
>4.167 ± 0.000 |
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Activity of 18 MMV Control Compounds against Sexual and Asexual Stages |
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Compound |
Viability INDEX |
EC50 (μM) |
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Stage I |
Stage II |
Stage III |
Stage IV |
Stage V |
Stage Asex |
Stage I |
Stage III |
Stage V |
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MMV000442 |
0.12 |
0.192 |
0.385 |
0.633 |
0.442 |
0.362a |
0.553 ± 0.041 |
>10.000 ±0.000 |
>10.000 ±0.000 |
MMV665971 |
0.056 |
0.097 |
0.137 |
0.171 |
0.416 |
0.489a |
0.746 ± 0.116 |
>10.000 ±0.000 |
>10.000 ±0.000 |
MMV011438 |
0.005 |
0.005 |
0.015 |
0 |
0 |
0.327a, 0.332b |
1.120 ± 0.116 |
2.428 ±0.620 |
4.225 ±0.609 |
MMV000248 |
0.006 |
0.057 |
0.061 |
0.085 |
0.121 |
0.719a |
1.058 ± 0.026 |
3.074 ±0.533 |
3.700 ±0.173 |
MMV666125 |
0.006 |
0.002 |
0.071 |
0.196 |
0.234 |
0.381a, 2.844b |
0.094 ± 0.068 |
1.342 ±0.259 |
6.154 ±0.569 |
MMV019918 |
0.017 |
0.014 |
0.01 |
0.015 |
0.033 |
0.800a |
1.264 ± 0.145 |
0.576 ±0.069 |
1.463 ±0.296 |
MMV019266 |
0.028 |
0.014 |
0.035 |
0.082 |
0.066 |
0.615a |
0.935 ± 0.214 |
1.372 ±0.210 |
1.743 ±0.206 |
MMV396797 |
0.034 |
0.007 |
0.033 |
0.094 |
0.077 |
0.477a |
5.435 ± 0.470 |
2.094 ±0.424 |
3.477 ±0.175 |
MMV667491 |
0.037 |
0.048 |
0.034 |
0.032 |
0 |
1.230a |
0.980 ± 0.069 |
0.667 ±0.101 |
0.596 ±0.085 |
MMV019881 |
0.063 |
0.065 |
0.039 |
0.047 |
0.013 |
0.646a |
3.048 ± 3.278 |
8.408 ±1.577 |
0.721 ±0.141 |
MMV000448 |
0.066 |
0.016 |
0.083 |
0.201 |
0.231 |
0.235a, 0.033b |
1.195 ± 0.113 |
5.356 ±0.612 |
4.652 ±0.394 |
MMV665882 |
0.116 |
0.092 |
0.122 |
0.168 |
0.13 |
0.466a |
0.180 ± 0.036 |
1.477 ±0.136 |
0.984 ±0.022 |
MMV665941 |
0.157 |
0.02 |
0.095 |
0.061 |
0.11 |
0.255a |
0.388 ± 0.035 |
2.271 ±0.751 |
1.044 ±0.040 |
MMV665980 |
0.24 |
0.184 |
0.087 |
0.108 |
0.247 |
0.211b |
>10.000 ± 0.000 |
9.350 ±3.237 |
6.612 ±1.100 |
MMV007116 |
0.377 |
0.505 |
0.734 |
0.733 |
0.846 |
0.351a, 0.716b |
>10.000 ± 0.000 |
>10.000 ±0.000 |
>10.000 ±0.000 |
MMV665827 |
0.592 |
0.9 |
0.81 |
0.769 |
0.791 |
0.119a, 0.166b |
>10.000 ± 0.000 |
>10.000 ±0.000 |
>10.000 ±0.000 |
MMV666021 |
0.61 |
0.871 |
0.74 |
0.897 |
1.055 |
0.094a, 1.998b |
>10.000 ± 0.000 |
>10.000 ±0.000 |
>10.000 ±0.000 |
MMV020492 |
0.768 |
0.756 |
0.97 |
0.912 |
0.989 |
0.026a |
>10.000 ± 0.000 |
>10.000 ±0.000 |
>10.000 ±0.000 |
The viability index shows the ratio for each gametocyte stage (I–V) compared to DMSO-treated control wells screened at 12.5 μM (384-well TSSA). EC50 values for stage I, III, and V, gametocytes are displayed as mean ± SD (1,536-well SaLSSA, in duplicate). Asexual stage data for 3D7 parasites as provided by MMV and the ChEMBL-NTD repository (https://www.ebi.ac.uk/chemblntd). |
a72 hr DAPI assay (Duffy and Avery, 2012). |
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b72 hr SYBR green assay |
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