Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum
Abstract
:1. Introduction
2. Materials and Methods
2.1. Organoarsenic Compound As-1–As-11 Synthesis
2.2. Parasite Culture
2.3. Malstat Assay
2.4. Stage-Specific Inhibition Assay
2.5. Gametocyte Toxicity Assay
2.6. Exflagellation Inhibition Assay
2.7. Hemolysis Assay
2.8. Cytotoxicity Assay
3. Results
3.1. Organoarsenic Compounds
3.2. The Organosarsenic Compounds Exhibit Antimalarial Activity
3.3. Organoarsenic Compounds Inhibit Different Asexual Blood Stages of the Malaria Parasite
3.4. Treatment with Organoarsenic Compounds Affects Gametocyte Development
3.5. The Organoarsenic Compounds Inhibit Exflagellation
3.6. The Organoarsenic Compounds Exhibit No Hemolytic or Cytotoxic Effect on Human cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
CQ | Chloroquine |
IC50 | Half maximal inhibitory concentration |
IC90 | 90% inhibitory concentration |
RT | Room temperature |
DMSO | Dimethyl sulfoxide |
APAD | 3-Acetylpyridine adenine dinucleotide |
LDH | Lactate dehydrogenase |
NBT | Nitro Blue Tetrazolium |
TLCK | Tosyl-l-lysyl-chloromethane hydrochloride |
INT | 2-[4-idophenyl]-3-[4-nitrophenyl]-5-phenyltetrazolium chloride |
SI | Selectivity index |
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Compounds | IC50 [µM] | IC90 [µM] | CC50 [µM] | SI |
---|---|---|---|---|
CQ-sensitive 3D7 | ||||
CQ | 0.002 ± 0.0003 | 0.0189 | ||
As-1 | - | - | ||
As-2 | 8.63 ± 0.606 | 77.67 | >100 | >12 |
As-3 | - | - | ||
As-4 | 8.64 ± 0.963 | 77.76 | >100 | >12 |
As-5 | 16.57 ± 3.092 | 149.13 | ||
As-6 | 7.55 ± 0.580 | 67.95 | >100 | >13 |
As-7 | 7.64 ± 0.387 | 68.76 | >100 | >13 |
As-8 | 1.52 ± 0.089 | 13.68 | >100 | >66 |
As-9 | 45.65 ± 0.435 | 410.85 | ||
As-10 | 18.13 ± 2.996 | 163.17 | ||
As-11 | 43.04 ± 5.700 | 387.36 | ||
CQ-resistant Dd2 | ||||
CQ | 0.28 ± 0.022 | 2.52 | ||
As-2 | 7.88 ± 0.261 | 70.92 | >100 | >13 |
As-4 | 30.05 ± 2.071 | 270.45 | >100 | >3 |
As-6 | 8.27 ± 1.330 | 74.43 | >100 | >12 |
As-7 | 34.92 ± 2.120 | 314.28 | >100 | >3 |
As-8 | 0.35 ± 0.099 | 3.15 | >100 | >286 |
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Basova, S.; Wilke, N.; Koch, J.C.; Prokop, A.; Berkessel, A.; Pradel, G.; Ngwa, C.J. Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum. Biomedicines 2020, 8, 260. https://doi.org/10.3390/biomedicines8080260
Basova S, Wilke N, Koch JC, Prokop A, Berkessel A, Pradel G, Ngwa CJ. Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum. Biomedicines. 2020; 8(8):260. https://doi.org/10.3390/biomedicines8080260
Chicago/Turabian StyleBasova, Sofia, Nathalie Wilke, Jan Christoph Koch, Aram Prokop, Albrecht Berkessel, Gabriele Pradel, and Che Julius Ngwa. 2020. "Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum" Biomedicines 8, no. 8: 260. https://doi.org/10.3390/biomedicines8080260