Articles de revues : « Sulfadoxine »

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&NA;. « Sulfadoxine see Pyrimethamine + sulfadoxine ». Reactions Weekly &NA;, n^o 294 (mars 1990) : 12. http://dx.doi.org/10.2165/00128415-199002940-00050.

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&NA;. « Sulfadoxine see Pyrimethamine + sulfadoxine ». Reactions Weekly &NA;, n^o 296 (avril 1990) : 7. http://dx.doi.org/10.2165/00128415-199002960-00031.

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&NA;. « Sulfadoxine see Pyrimethamine + sulfadoxine ». Reactions Weekly &NA;, n^o 340 (mars 1991) : 7. http://dx.doi.org/10.2165/00128415-199103400-00029.

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&NA;. « Pyrimethamine + sulfadoxine ». Reactions Weekly &NA;, n^o 294 (mars 1990) : 12. http://dx.doi.org/10.2165/00128415-199002940-00047.

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&NA;. « Pyrimethamine + sulfadoxine ». Reactions Weekly &NA;, n^o 296 (avril 1990) : 7. http://dx.doi.org/10.2165/00128415-199002960-00027.

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&NA;. « Pyrimethamine/sulfadoxine ». Reactions Weekly &NA;, n^o 1043 (mars 2005) : 17. http://dx.doi.org/10.2165/00128415-200510430-00057.

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&NA;. « Pyrimethamine + sulfadoxine ». Reactions Weekly &NA;, n^o 340 (mars 1991) : 7. http://dx.doi.org/10.2165/00128415-199103400-00027.

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&NA;. « Pyrimethamine/sulfadoxine ». Reactions Weekly &NA;, n^o 1401 (mai 2012) : 32. http://dx.doi.org/10.2165/00128415-201214010-00121.

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Korsinczky, Michael, Katja Fischer, Nanhua Chen, Joanne Baker, Karl Rieckmann et Qin Cheng. « Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site ». Antimicrobial Agents and Chemotherapy 48, n^o 6 (juin 2004) : 2214–22. http://dx.doi.org/10.1128/aac.48.6.2214-2222.2004.

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ABSTRACT Sulfadoxine is predominantly used in combination with pyrimethamine, commonly known as Fansidar, for the treatment of Plasmodium falciparum. This combination is usually less effective against Plasmodium vivax, probably due to the innate refractoriness of parasites to the sulfadoxine component. To investigate this mechanism of resistance by P. vivax to sulfadoxine, we cloned and sequenced the P. vivax dhps (pvdhps) gene. The protein sequence was determined, and three-dimensional homology models of dihydropteroate synthase (DHPS) from P. vivax as well as P. falciparum were created. The docking of sulfadoxine to the two DHPS models allowed us to compare contact residues in the putative sulfadoxine-binding site in both species. The predicted sulfadoxine-binding sites between the species differ by one residue, V585 in P. vivax, equivalent to A613 in P. falciparum. V585 in P. vivax is predicted by energy minimization to cause a reduction in binding of sulfadoxine to DHPS in P. vivax compared to P. falciparum. Sequencing dhps genes from a limited set of geographically different P. vivax isolates revealed that V585 was present in all of the samples, suggesting that V585 may be responsible for innate resistance of P. vivax to sulfadoxine. Additionally, amino acid mutations were observed in some P. vivax isolates in positions known to cause resistance in P. falciparum, suggesting that, as in P. falciparum, these mutations are responsible for acquired increases in resistance of P. vivax to sulfadoxine.

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&NA;. « Antiretrovirals/pyrimethamine/sulfadoxine ». Reactions Weekly &NA;, n^o 1318 (septembre 2010) : 11. http://dx.doi.org/10.2165/00128415-201013180-00031.

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Amukoye, E., P. A. Winstanley, W. M. Watkins, R. W. Snow, J. Hatcher, M. Mosobo, E. Ngumbao et al. « Chlorproguanil-dapsone : effective treatment for uncomplicated falciparum malaria. » Antimicrobial Agents and Chemotherapy 41, n^o 10 (octobre 1997) : 2261–64. http://dx.doi.org/10.1128/aac.41.10.2261.

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Pyrimethamine-sulfadoxine, the first choice for uncomplicated falciparum malaria in Africa, exerts strong selection pressure for resistance because of its slow elimination. It is likely that resistance will emerge rapidly, and there is no widely affordable replacement. Chlorproguanil-dapsone is cheap, rapidly eliminated, more potent than pyrimethamine-sulfadoxine, and could be introduced in the near future to delay the onset of antifolate resistance and as "salvage therapy" for pyrimethamine-sulfadoxine failure. A total of 448 children were randomly allocated (double blind) to either a single dose of pyrimethamine-sulfadoxine or to one of two chlorproguanil-dapsone regimens: a single dose or three doses at 24-h intervals. Reinfections are clinically indistinguishable from recrudescence and are more likely after treatment with rapidly eliminated drugs; we measured the incidence of parasitemia in 205 initially aparasitemic children to allow comparison with the three treatment groups. The patients and a community surveillance group were followed up for 28 days. At the study end point, 31.2% (95% confidence interval, 24.9-38.0) of the community surveillance group subjects were parasitemic, compared with subjects in the treatment groups, whose rates of parasitemia were 40.8% (32.9-49.0; relative risk [RR], 1.31 [0.99-1.73]) after triple-dose chlorproguanil-dapsone, 19.7% (13.5-27.2; RR, 0.63 [0.43-0.93]) after pyrimethamine-sulfadoxine, and 65.6% (57.5-73.0; RR, 2.10 [1.66-2.65]) after single-dose chlorproguanil-dapsone. Pyrimethamine-sulfadoxine and triple-dose chlorproguanil-dapsone were effective treatments. Pyrimethamine-sulfadoxine provided chemoprophylaxis during follow-up because of its slow elimination. Triple-dose chlorproguanil-dapsone should now be developed in an attempt to reduce the rate of emergence of antifolate resistance in Africa and for affordable salvage therapy in cases of pyrimethamine-sulfadoxine failure.

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Ganguly, Swagata, Pabitra Saha, Moytrey Chatterjee et Ardhendu K. Maji. « Prevalence of Polymorphisms in Antifolate Drug Resistance Molecular Marker Genespvdhfrandpvdhpsin Clinical Isolates of Plasmodium vivax from Kolkata, India ». Antimicrobial Agents and Chemotherapy 58, n^o 1 (21 octobre 2013) : 196–200. http://dx.doi.org/10.1128/aac.01171-13.

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ABSTRACTSulfadoxine-pyrimethamine has never been recommended for the treatment ofPlasmodium vivaxmalaria as the parasite is intrinsically resistant to pyrimethamine. The combination was introduced as a promising agent to treatPlasmodium falciparummalaria in many countries but was withdrawn after a few years due to development and spread of resistant strains. Presently, sulfadoxine-pyrimethamine is used as a partner drug of artemisinin-based combination therapy to treat uncomplicated falciparum malaria, and a combination of artesunate-sulfadoxine-pyrimethamine is currently in use in India. In countries like India, where bothP. vivaxandP. falciparumare equally prevalent, some proportion ofP. vivaxbacteria is exposed to sulfadoxine-pyrimethamine due to misdiagnosis and mixed infections. As reports on thein vivotherapeutic efficacy of sulfadoxine-pyrimethamine inP. vivaxare rare, the study of mutations in the marker genesP. vivaxdhfr(pvdhfr) andpvdhpsis important for predicting drug selection pressure and sulfadoxine-pyrimethamine resistance monitoring. We studied the prevalence of point mutations and haplotypes of both the genes in 80P. vivaxisolates collected from urban Kolkata, India, by the DNA sequencing method. Point mutation rates in both the genes were low. The double mutantpvdhfrA15N50R58N117I173(mutations are in boldface) and the single mutantpvdhpsgenotype S382G383K512A553V585were more prevalent, while 35% of the isolates harbored the wild-type genotype. The triple mutant ANRNI-SGKAV was found in 29.9% isolates. No quintuple mutant genotype was recorded. TheP. vivaxparasites in urban Kolkata may still be susceptible to sulfadoxine-pyrimethamine. Hence, a combination of antimalarial drugs like artesunate-sulfadoxine-pyrimethamine introduced forP. falciparuminfection might be effective inP. vivaxinfection also. Study of the therapeutic efficacy of this combination inP. vivaxis thus strongly suggested. (The study protocol was registered in the Clinical Trial Registry-India [CTRI] of the Indian Council of Medical Research under registration number CTRI/2011/09/002031.)

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&NA;. « Mefloquine/sulfadoxine/pyrimethamine overdose ». Reactions Weekly &NA;, n^o 448 (avril 1993) : 11. http://dx.doi.org/10.2165/00128415-199304480-00050.

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Muhammad, Andry, De Lux Effendy et Putra Muchlisyam. « Simultaneously Content Analysis of Sulfadoxine and Pyrimethamine in Tablet Dosage Form by Spectrophotometry Ultraviolet with Dual Wavelenght Method ». Asian Journal of Pharmaceutical Research and Development 7, n^o 4 (14 août 2019) : 34–37. http://dx.doi.org/10.22270/ajprd.v7i4.555.

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Aim: method development results from this study are expected to be one of the methods that can be applied by the relevant agencies in determining the simultaneous levels of sulfadoxine and pyrimethamine in tablet dosage form. Pyrimethamine - Sulfadoxine (PS) is an anti-malarial drug combination sulfonamide group / sulfone with nature skizontosida diaminopirimidine network, these drugs are very practical because it can be given in a single dose, and however, this combination provides a new challenge for the pharmaceutical industry in connection with the development of new analytical methods in the determination of levels. Methods: The study was carried out experimentally by spectrophotometric method is the method of multiple wavelengths and then tested for validity based validation parameters, namely linearity, accuracy, precision, LOD and LOQ and intraday and inter day. Then, the method is tested on dosage tablets containing pyrimethamine and sulfadoxine that are on the market. Results: The results showed that the application of the method of multiple wavelengths at a concentration carried out at λ 284.8 nm and 258.8 nm to pyrimethamine and at λ 274.2 nm and 291.6 nm to sulfadoxine. Research results successfully applied the method dual wavelength which is successfully applied to determining the concentration of pyrimethamine and sulfadoxine simultaneously in a tablet.

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White, Nicholas. « Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria : Sulfadoxine-pyrimethamine is not working in Malawi ». BMJ 328, n^o 7450 (20 mai 2004) : 1259.1. http://dx.doi.org/10.1136/bmj.328.7450.1259.

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MENARD, DIDIER, MAX ROGER KOULA, ANTOINE TALARMIN, NESTOR MADJI, ALEXANDRE MANIRAKIZA et DJIBRINE DJALLE. « EFFICACY OF CHLOROQUINE, AMODIAQUINE, SULFADOXINE-PYRIMETHAMINE, CHLOROQUINE-SULFADOXINE-PYRIMETHAMINE COMBINATION, AND AMODIAQUINE-SULFADOXINE-PYRIMETHAMINE COMBINATION IN CENTRAL AFRICAN CHILDREN WITH NONCOMPLICATED MALARIA ». American Journal of Tropical Medicine and Hygiene 72, n^o 5 (1 mai 2005) : 581–85. http://dx.doi.org/10.4269/ajtmh.2005.72.581.

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Mockenhaupt, Frank P., George Bedu-Addo, Claudia Junge, Lena Hommerich, Teunis A. Eggelte et Ulrich Bienzle. « Markers of Sulfadoxine-Pyrimethamine-Resistant Plasmodium falciparum in Placenta and Circulation of Pregnant Women ». Antimicrobial Agents and Chemotherapy 51, n^o 1 (6 novembre 2006) : 332–34. http://dx.doi.org/10.1128/aac.00856-06.

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ABSTRACT Placental sequestration of Plasmodium falciparum in pregnancy may impair the usefulness of molecular markers of sulfadoxine-pyrimethamine resistance. In 300 infected, delivering women, the concordance of PCR-restriction fragment length polymorphism-derived parasite resistance alleles in matched samples from placenta and circulation was 83 to 98%. Sulfadoxine-pyrimethamine resistance typing in peripheral blood is reasonably representative of P. falciparum infecting pregnant women.

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Basco, Leonardo K., Rachida Tahar et Pascal Ringwald. « Molecular Basis of In Vivo Resistance to Sulfadoxine-Pyrimethamine in African Adult Patients Infected withPlasmodium falciparum Malaria Parasites ». Antimicrobial Agents and Chemotherapy 42, n^o 7 (1 juillet 1998) : 1811–14. http://dx.doi.org/10.1128/aac.42.7.1811.

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ABSTRACT In vitro sulfadoxine and pyrimethamine resistance has been associated with point mutations in the dihydropteroate synthase and dihydrofolate reductase domains, respectively, but the in vivo relevance of these point mutations has not been well established. To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and followed up for 28 days. After losses to follow-up (n = 1) or elimination of DNA samples due to mixed parasite populations with pyrimethamine-sensitive and pyrimethamine-resistant profiles (n = 3), parasite genomic DNA from day 0 blood samples of six patients were analyzed by DNA sequencing. Three patients who were cured had isolates characterized by a wild-type or mutant dihydrofolate reductase gene (with one or two mutations) and a wild-type dihydropteroate synthase gene. Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment carried isolates with triple dihydrofolate reductase gene mutations and either a wild-type or a mutant dihydropteroate synthase gene. Three dihydrofolate reductase gene codons (51, 59, and 108) may be reliable genetic markers that can accurately predict the clinical outcome of sulfadoxine-pyrimethamine treatment in Africa.

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Kerr, Cathel. « Sulfadoxine-pyrimethamine still confers benefit ». Lancet Infectious Diseases 7, n^o 8 (août 2007) : 510. http://dx.doi.org/10.1016/s1473-3099(07)70174-3.

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Peters, W. « Mefloquine/sulfadoxine/pyrimethamine for malaria ». Transactions of the Royal Society of Tropical Medicine and Hygiene 89, n^o 6 (novembre 1995) : 699. http://dx.doi.org/10.1016/0035-9203(95)90452-2.

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Stürchler, D., J. Handschin, S. Mannino, M. L. Mittelholzer, William Rooney et Krongthong Thimasarn. « Mefloquine plus sulfadoxine and pyrimethamine ». Lancet 338, n^o 8758 (juillet 1991) : 51–52. http://dx.doi.org/10.1016/0140-6736(91)90037-p.

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Watt, G., et G. D. Shanks. « Pyrimethamine/sulfadoxine for falciparum malaria ». Lancet 338, n^o 8768 (septembre 1991) : 700–701. http://dx.doi.org/10.1016/0140-6736(91)91281-x.

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Win, Kyaw, Tin Thein Lwin, Yeye Thwe et Khin Win. « COMBINATION OF MEFLOQUINE WITH SULFADOXINE-PYRIMETHAMINE COMPARED WITH TWO SULFADOXINE-PYRIMETHAMINE COMBINATIONS IN MALARIA CHEMOPROPHYLAXIS ». Lancet 326, n^o 8457 (septembre 1985) : 694–95. http://dx.doi.org/10.1016/s0140-6736(85)92933-2.

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Daniel, P. T., J. Holzschuh et P. A. Berg. « Sulfadoxine specific lymphocyte transformation in a patient with eosinophilic pneumonia induced by sulfadoxine-pyrimethamine (Fansidar). » Thorax 44, n^o 4 (1 avril 1989) : 307–9. http://dx.doi.org/10.1136/thx.44.4.307.

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Terlouw, Dianne J., Bernard L. Nahlen, Jeanne M. Courval, Simon K. Kariuki, Oren S. Rosenberg, Aggrey J. Oloo, Margarette S. Kolczak, William A. Hawley, Altaf A. Lal et Feiko O. ter Kuile. « Sulfadoxine-Pyrimethamine in Treatment of Malaria in Western Kenya : Increasing Resistance and Underdosing ». Antimicrobial Agents and Chemotherapy 47, n^o 9 (septembre 2003) : 2929–32. http://dx.doi.org/10.1128/aac.47.9.2929-2932.2003.

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ABSTRACT Between 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1,175 children aged <24 months receiving 2,789 treatments for falciparum malaria in western Kenya using a widely deployed age-based dose regimen: infants, 125 plus 6.25 mg (sulfadoxine plus pyrimethamine); children aged 12 to 23 months; 250 plus 12.5 mg. Cumulative treatment failure by day 7, defined as early clinical failure by day 3 or presence of parasitemia on day 7, increased from 18% in 1993 to 1994 to 22% in 1997 to 1998 (P-trend test = 0.20). Based on body weight, the median dose received was 20 plus 1.00 mg/kg, and 73% of the treatments were given at lower than the recommended target dose of 25 plus 1.25 mg/kg. Underdosing accounted for 26% of cumulative treatment failures. After the dose was increased in 1998 (median, 36 plus 1.8 mg/kg), only 4.2% of patients received less than 25 plus 1.25 mg/kg and there was no association with treatment failure. However, the proportion of cumulative treatment failure continued to increase to 27% by 1999 (P-trend test = 0.03). These results raise concern about the longevity of sulfadoxine-pyrimethamine in these settings. Underdosing may have contributed to the rate at which sulfadoxine-pyrimethamine resistance developed in this area. Treatment guidelines should ensure that adequate doses are given from the initial deployment of antimalarials onward.

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Hayton, Karen, Lisa C. Ranford-Cartwright et David Walliker. « Sulfadoxine-Pyrimethamine Resistance in the Rodent Malaria Parasite Plasmodium chabaudi ». Antimicrobial Agents and Chemotherapy 46, n^o 8 (août 2002) : 2482–89. http://dx.doi.org/10.1128/aac.46.8.2482-2489.2002.

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ABSTRACT We have studied resistance to sulfadoxine-pyrimethamine (S/P) in the rodent malaria parasite Plasmodium chabaudi. A stable S/P-resistant mutant, AS(50S/P), was selected by drug treatment of a clone, AS(PYR), already resistant to pyrimethamine. The sequences of the P. chabaudi dhfr and dhps genes were obtained and found to be identical in AS(50S/P) and AS(PYR), showing that resistance to S/P in AS(50S/P) was not due to additional mutations in either gene. AS(50S/P) was crossed with a drug-sensitive clone, AJ, and 16 independent recombinant progeny were obtained. These clones were phenotyped for their susceptibility to S/P and to sulfadoxine and pyrimethamine separately. Pyrimethamine resistance was invariably associated with S/P resistance, but no correlation was found between resistance to S/P and resistance to sulfadoxine. Quantitative trait locus analysis of the progeny with 31 chromosome-specific markers showed that mutant P. chabaudi dhfr, or one or more genes closely linked to it, was a major determinant of S/P resistance. In addition, the inheritance of genes on chromosomes 5 and 13 from the sensitive parent appeared to contribute to the level of resistance observed. These results demonstrate that the S/P resistance of the AS(50S/P) mutant of P. chabaudi does not involve mutation in dhps and is not due simply to a combination of two genes determining resistance to pyrimethamine and sulfadoxine separately.

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&NA;. « Kenyan children benefit from pyrimethamine/sulfadoxine ». Inpharma Weekly &NA;, n^o 1647 (juillet 2008) : 13. http://dx.doi.org/10.2165/00128413-200816470-00044.

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Goel, Divya, Shafiqa Aslam, Rani Walia et Akshay Sadhotra. « Artesunate-, sulfadoxine-, and pyrimethamine-induced cardiotoxicity ». BLDE University Journal of Health Sciences 1, n^o 1 (2016) : 54. http://dx.doi.org/10.4103/2456-1975.183288.

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&NA;. « Pyrimethamine-sulfadoxine : assessment of adverse effects ». Reactions Weekly &NA;, n^o 701 (mai 1998) : 5. http://dx.doi.org/10.2165/00128415-199807010-00008.

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&NA;. « Pyrimethamine/sulfadoxine an effective intermittent antimalarial ». Inpharma Weekly &NA;, n^o 1288 (mai 2001) : 12. http://dx.doi.org/10.2165/00128413-200112880-00024.

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&NA;. « Amodiaquine + pyrimethamine/sulfadoxine best for malaria ? » Inpharma Weekly &NA;, n^o 1300 (août 2001) : 9. http://dx.doi.org/10.2165/00128413-200113000-00021.

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Peters, Philip J., Michael C. Thigpen, Monica E. Parise et Robert D. Newman. « Safety and Toxicity of Sulfadoxine/Pyrimethamine ». Drug Safety 30, n^o 6 (2007) : 481–501. http://dx.doi.org/10.2165/00002018-200730060-00003.

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&NA;. « Pyrimethamine/sulfadoxine given intermittently reduces malaria ». Inpharma Weekly &NA;, n^o 1508 (octobre 2005) : 10. http://dx.doi.org/10.2165/00128413-200515080-00020.

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&NA;. « Effective toxoplasmosis prophylaxis with pyrimethamine/sulfadoxine ». Inpharma Weekly &NA;, n^o 955 (septembre 1994) : 14. http://dx.doi.org/10.2165/00128413-199409550-00026.

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Divala, Titus H., Lauren M. Cohee et Miriam K. Laufer. « The remarkable tenacity of sulfadoxine-pyrimethamine ». Lancet Infectious Diseases 19, n^o 5 (mai 2019) : 460–61. http://dx.doi.org/10.1016/s1473-3099(18)30796-5.

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Chemla, Cathy, et Isabelle Villena. « Sulfadoxine–Pyrimethamine Combination in Congenital Toxoplasmosis ». Pediatric Infectious Disease Journal 36, n^o 3 (mars 2017) : 349–50. http://dx.doi.org/10.1097/inf.0000000000001435.

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&NA;. « Pyrimethamine/sulfadoxine dosing makes a difference ». Inpharma Weekly &NA;, n^o 1553 (septembre 2006) : 16. http://dx.doi.org/10.2165/00128413-200615530-00043.

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RWAGACONDO, CLAUDE E., CHANTAL VAN OVERMEIR, CORINE KAREMA, JEF VAN DEN ENDE, FRANCOIS NIYITEGEKA, VERONIQUE MUGISHA, JOSEPH SARUSHI, UMBERTO D’ALESSANDRO et JEAN-CLAUDE DUJARDIN. « EFFICACY OF AMODIAQUINE ALONE AND COMBINED WITH SULFADOXINE-PYRIMETHAMINE AND OF SULFADOXINE PYRIMETHAMINE COMBINED WITH ARTESUNATE ». American Journal of Tropical Medicine and Hygiene 68, n^o 6 (1 juin 2003) : 743–47. http://dx.doi.org/10.4269/ajtmh.2003.68.743.

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Mohamed, Hagga M. A., Mohd Imran, Monadil H. M. Ali, Mohammed F. Abdelwahab et Abdullrahman A. Alhaj. « A UV-Spectrophotmetric Chemometric Method for the Simultaneous Determination of Sulfadoxine and Pyrimethamine in Tablets ». Asian Journal of Pharmaceutical Research and Health Care 8, n^o 3 (23 juin 2016) : 76. http://dx.doi.org/10.18311/ajprhc/2016/3965.

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<p style="margin: 0in 0in 0pt; text-align: justify; line-height: 150%;"><span style="line-height: 150%; font-family: 'Times New Roman','serif'; font-size: 12pt; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi;">In the present study, a simple, inexpensive, precise and accurate uv-spectrophotometric method based on chemometrics, has been developed for the simultaneous determination of sulfadoxine and pyrimethamine in tablet formulation. The % recoveries obtained were 99.7% ± 0.9 and 101.5% ± 0.8 for sulfadoxine and pyrimethamine, respectively. The developed method has been compared to USP-HPLC method with regard to accuracy and precision. The calculated F-ratio and the (t) statistics indicate that there is no significant difference at 5% level with regard to precision and accuracy between the proposed and the USP methods. Moreover, the developed method is simple, cost-effective, and less time-consuming. Accordingly, it can be used advantageously in routine quality control of sulfadoxine and pyrimethamine in tablet formulation. </span></p>

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C. S. Pinheiro, Luiz, Lívia M. Feitosa, Marilia O. Gandi, Flávia F. Silveira et Nubia Boechat. « The Development of Novel Compounds Against Malaria : Quinolines, Triazolpyridines, Pyrazolopyridines and Pyrazolopyrimidines ». Molecules 24, n^o 22 (13 novembre 2019) : 4095. http://dx.doi.org/10.3390/molecules24224095.

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Based on medicinal chemistry tools, new compounds for malaria treatment were designed. The scaffolds of the drugs used to treat malaria, such as chloroquine, primaquine, amodiaquine, mefloquine and sulfadoxine, were used as inspiration. We demonstrated the importance of quinoline and non-quinoline derivatives in vitro with activity against the W2 chloroquine-resistant (CQR) Plasmodium falciparum clone strain and in vivo against Plasmodium berghei-infected mouse model. Among the quinoline derivatives, new hybrids between chloroquine and sulfadoxine were designed, which gave rise to an important prototype that was more active than both chloroquine and sulfadoxine. Hybrids between chloroquine–atorvastatin and primaquine–atorvastatin were also synthesized and shown to be more potent than the parent drugs alone. Additionally, among the quinoline derivatives, new mefloquine derivatives were synthesized. Among the non-quinoline derivatives, we obtained excellent results with the triazolopyrimidine nucleus, which gave us prototype I that inspired the synthesis of new heterocycles. The pyrazolopyrimidine derivatives stood out as non-quinoline derivatives that are potent inhibitors of the P. falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. We also examined the pyrazolopyridine and pyrazolopyrimidine nuclei.

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Dzinjalamala, Fraction K., Allan Macheso, James G. Kublin, Terrie E. Taylor, Karen I. Barnes, Malcolm E. Molyneux, Christopher V. Plowe et Peter J. Smith. « Association between the Pharmacokinetics and In Vivo Therapeutic Efficacy of Sulfadoxine-Pyrimethamine in Malawian Children ». Antimicrobial Agents and Chemotherapy 49, n^o 9 (septembre 2005) : 3601–6. http://dx.doi.org/10.1128/aac.49.9.3601-3606.2005.

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ABSTRACT Sulfadoxine-pyrimethamine (SP) has been widely used in recent years to treat acute uncomplicated Plasmodium falciparum malaria. Risk factors for SP therapeutic failure include young age, subtherapeutic SP concentrations, and resistance-conferring genetic mutations in parasite target enzymes. A substantial proportion of patients are able to clear genetically highly resistant P. falciparum genotypes. To determine whether blood SP concentrations independently affect the patient's ability to clear resistant genotypes, we compared SP pharmacokinetics of cases of adequate clinical and parasitological response (ACPR) with cases of treatment failure (TF). When patients with ACPR and TF were compared, mean values were similar for the day 3 blood pyrimethamine (205 ng/ml versus 172 ng/ml; P = 0.25) and estimated maximum sulfadoxine (79 ± 6.52 versus 69 ± 6.27 μg/ml; P = 0.60) concentrations, for sulfadoxine terminal-phase elimination half-lives (7.15 versus 6.41 days; P = 0.42), and for the extents of sulfadoxine absorption (areas under the concentration-time curve of 932 ± 100 versus 888 ± 78.9 μg day ml−1; P = 0.72). Among patients infected with the quintuple resistant parasites, day 3 blood pyrimethamine concentrations were higher in those who cleared the infection than in those who did not (305 ± 35.4 versus 228 ± 21.7 ng/ml; P = 0.037). Within this subgroup, this finding remained significant after adjusting for endogenous folate levels, age, site, and resistance-conferring mutations (odds ratio: 1.011 [1.003 to 1.024]; P = 0.018). However, as a subgroup analysis, our biologically plausible observation that higher blood pyrimethamine concentrations enhance the ability of patients to clear resistant P. falciparum should be interpreted with caution and needs further validation.

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Bourée, P. « Résistance à la sulfadoxine-pyriméthamine et grossesse ». Médecine et Santé Tropicales 22, n^o 4 (octobre 2012) : 371. http://dx.doi.org/10.1684/mst.2012.0119.

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&NA;. « Pyrimethamine/sulfadoxine effective primary prophylaxis in HIV ». Inpharma Weekly &NA;, n^o 1348 (juillet 2002) : 17. http://dx.doi.org/10.2165/00128413-200213480-00037.

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&NA;. « Amodiaquine + pyrimethamine/sulfadoxine for malaria in Uganda ». Inpharma Weekly &NA;, n^o 1499 (août 2005) : 18. http://dx.doi.org/10.2165/00128413-200514990-00053.

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&NA;. « Isoniazid plus pyrimethamine/sulfadoxine : reduction in morbidity ». Inpharma Weekly &NA;, n^o 1219 (janvier 2000) : 18. http://dx.doi.org/10.2165/00128413-200012190-00035.

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Arnold, Keith. « MEFLOQUINE AND SULFADOXINE/ PYRIMETHAMINE RESISTANT PLASMODIUM FALCIPARUM ». Lancet 327, n^o 8473 (janvier 1986) : 154. http://dx.doi.org/10.1016/s0140-6736(86)92287-7.

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&NA;. « Pyrimethamine/sulfadoxine : durable efficacy in falciparum malaria ». Inpharma Weekly &NA;, n^o 1424 (février 2004) : 11. http://dx.doi.org/10.2165/00128413-200414240-00026.

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Sharma, Sangita, Madhurjya Neog, Vipul Prajapati, Hiren Patel et Dipti Dabhi. « Spectrophotometric Estimation of Sulfadoxine in Pharmaceutical Preparations ». E-Journal of Chemistry 7, n^o 4 (2010) : 1246–53. http://dx.doi.org/10.1155/2010/289723.

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Four simple, sensitive, accurate and rapid visible spectrophotometric methods (A, B, C and D) have been developed for the estimation of sulfadoxine in pharmaceutical preparations. They are based on the diazotization of sulfadoxine with sodium nitrite and hydrochloric acid followed by coupling withN-(1-naphthyl) ethylenediamine dihydrochloride (Method A) to form pink coloured chromogen, diphenylamine (Method B) to form light pink coloured chromogen, chromotropic acid (in alkaline medium) (Method C) to form orange coloured chromogen, Resorcinol (in alkaline medium) (Method D) to form light orange coloured chromogen and exhibiting absorption maxima (λmax) at 536 nm, 524 nm, 520 nm and 496 nm respectively. The coloured chromogens formed are stable for more than 2 h. Beer’s law was obeyed in the concentration range of 1.0 - 5.0 μg/mL in Method A , 5.0 - 25.0 μg/mL in Method B, 5.0 - 25.0 μg/mL in Method C and 4.0 - 8.0 μg/mL in Method D respectively. The results of the three analysis have been validated statistically and by recovery studies. The results obtained in the proposed methods are in good agreements with labeled amounts, when marketed pharmaceutical preparations are analyzed.

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Dieckmann, Angela, et Albrecht Jung. « Mechanisms of sulfadoxine resistance in Plasmodium falciparum ». Molecular and Biochemical Parasitology 19, n^o 2 (mai 1986) : 143–47. http://dx.doi.org/10.1016/0166-6851(86)90119-2.

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White, Nicholas J. « Sulfadoxine-pyrimethamine for the treatment of malaria ». Transactions of the Royal Society of Tropical Medicine and Hygiene 85, n^o 4 (juillet 1991) : 556–57. http://dx.doi.org/10.1016/0035-9203(91)90261-v.

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