Combined Spatial Limitation around Residues 16 and 108 of Plasmodium falciparum Dihydrofolate Reductase Explains Resistance to Cycloguanil
نویسندگان
چکیده
منابع مشابه
Cycloguanil and its parent compound proguanil demonstrate distinct activities against Plasmodium falciparum malaria parasites transformed with human dihydrofolate reductase.
The lack of suitable antimalarial agents to replace chloroquine and pyrimethamine/sulfadoxine threatens efforts to control the spread of drug-resistant strains of the malaria parasite Plasmodium falciparum. Here we describe a transformation system, involving WR99210 selection of parasites transformed with either wild-type or methotrexate-resistant human dihydrofolate reductase (DHFR), that has ...
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Plasmodium falciparum strains bearing quadruple mutations of dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) at codons 51, 59, 108, and 164 are highly resistant to pyrimethamine (PYR), a diaminopyrimidine, but sensitive to WR99210 (WR), a cycloguanil analog, suggesting different enzyme-inhibitor binding interactions. A combination of these inhibitors to delay the onset of antifolate re...
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In vivo and in vitro assessments of the response of P. falciparum to chloroquine using WHO standard kits and techniques were carried out in I ran Shahr, Sistan and Baluchestan province of Iran in 1985. In the in vivo assessment, 24 malaria patients treated with chloroquine (25mg/kg over three days) were followed up for one to four weeks. The mean parasite clearance time was 4.3 days and in...
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The paper by Ochong et al. modifies the real-time PCR method we published previously and applies it to samples from Malawi, Zambia, and Thailand (2, 7). These authors bring up several criticisms of the original technique, and we welcome this opportunity to clarify concerns about this method. We would also like to comment on some of their conclusions. The primary criticism of Ochong et al. of ou...
متن کاملCharacteristics of genetic hitchhiking around dihydrofolate reductase gene associated with pyrimethamine resistance in Plasmodium falciparum isolates from India.
Sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum has been widespread across continents, causing the major hurdle of controlling malaria. Resistance is encoded mainly by point mutations in P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) target genes. To study the origin and evolution of pyrimethamine resistance on the Indian subcontinent, mi...
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ژورنال
عنوان ژورنال: Antimicrobial Agents and Chemotherapy
سال: 2012
ISSN: 0066-4804,1098-6596
DOI: 10.1128/aac.00301-12