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Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs
Abstract
A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy- d -xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in P. falciparum depends on the DOXP pathway. This pathway is probably located in the apicoplast. The recombinant P. falciparum DOXP reductoisomerase was inhibited by fosmidomycin and its derivative, FR-900098. Both drugs suppressed the in vitro growth of multidrug-resistant P. falciparum strains. After therapy with these drugs, mice infected with the rodent malaria parasite P. vinckei were cured.
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Citations
Cited by
Genome sequence of the human malaria parasite Plasmodium falciparum
Gardner, M. J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R. W., Carlton, J. M., Pain, A., Nelson, K. E., Bowman, S., et al. (2002) · Nature · doi:10.1038/nature01097 · Cited by 4,407
The influence of natural products upon drug discovery (Antiquity to late 1999)
Newman, D. J., Cragg, G. M., & Snader, K. M. (2000) · Natural Product Reports · doi:10.1039/a902202c · Cited by 1,293
Isoprenoid biosynthesis: The evolution of two ancient and distinct pathways across genomes
Lange, B. M., Rujan, T., Martin, W., & Croteau, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.240454797 · Cited by 881
Biosynthesis of isoprenoids via the non-mevalonate pathway
Eisenreich, W., Bacher, A., Arigoni, D., & Rohdich, F. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-3381-z · Cited by 668
Estévez, J. M., Cantero, A., Reindl, A., Reichler, S., & León, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100854200 · Cited by 668
Metadata
- Authors
- Jomaa, H., Wiesner, J., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Türbachova, I., Eberl, M., Zeidler, J., Lichtenthaler, H. K., Soldati, D., & Beck, E.
- Venue
- Science
- Published
- 1999-09-03
- Volume
- 285
- Issue
- 5433
- Pages
- 1573-1576
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2164267446
- Cited by
- 1,173
- References
- 0
- FWCI
- 67.23
- Type
- journal article
- Language
- en
- Open access
- closed
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- Jomaa, H., Wiesner, J., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Türbachova, I., Eberl, M., Zeidler, J., Lichtenthaler, H. K., Soldati, D., & Beck, E. (1999). Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs. Science. https://doi.org/10.1126/science.285.5433.1573
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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