The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria.
Open accessAbstract
Proguanil and pyrimethamine are antifolate drugs with distinct chemical structures that are used commonly in the prophylaxis and treatment of Plasmodium falciparum malaria. Clinical reports and field studies have suggested that some parasites refractory to proguanil can be treated with pyrimethamine, and vice versa. Analysis of the P. falciparum dihydrofolate reductase (DHFR) from different parasites reveals the structural basis for differential susceptibility to these antifolate drugs. Parasites harboring a pair of point mutations from Ala-16 to Val-16 and from Ser-108 to Thr-108 are resistant to cycloguanil (the active metabolite of proguanil) but not to pyrimethamine. A single Asn-108 mutation, on the other hand, confers resistance to pyrimethamine with only a moderate decrease in susceptibility to cycloguanil. Significant cross-resistance to both drugs occurs in parasites having mutations that include Ser-108----Asn-108 and Ile-164----Leu-164. These results reflect the distinct structures of pyrimethamine and cycloguanil and suggest fine differences in binding within the active site cavity of DHFR. Alternative inhibitors, used alone or in combination, may be effective against some strains of cycloguanil- or pyrimethamine-resistant malaria.
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Cited by
Mechanisms of Resistance of Malaria Parasites to Antifolates
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Current status of malaria and potential for control
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Preventing antimalarial drug resistance through combinations
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Metadata
- Authors
- Peterson, D. S., Milhous, W. K., & Wellems, T. E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1990-04
- Volume
- 87
- Issue
- 8
- Pages
- 3018-3022
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1976176203
- Cited by
- 419
- References
- 18
- FWCI
- 11.11
- Type
- journal article
- Language
- en
- Open access
- green
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- Peterson, D. S., Milhous, W. K., & Wellems, T. E. (1990). Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.87.8.3018
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
