Novel bis- and tris-1,2,4-trioxanes: Synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in swiss mice

Journal of Medicinal Chemistry

Volumn 51, Issue 23, 2008, Pages 7581-7592

  Singh, Chandan ^a   Verma, Ved Prakash ^a   Naikade, Niraj Krishna ^a   Singh, Ajit Shankar ^b   Hassam, Mohammad ^a   Puri, Sunil K ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 TRIOXANE DERIVATIVE; ARTEETHER; BIS 1,2,4 TRIOXANE DERIVATIVE; CYCLOHEXANE; CYCLOPENTANE; TRIS 1,2,4 TRIOXANE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; MALARIA; MOUSE; MULTIDRUG RESISTANCE; NONHUMAN; PLASMODIUM YOELII; SWISS WEBSTER MOUSE;

ANIMALS; ANTIMALARIALS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; DRUG RESISTANCE, MULTIPLE; HETEROCYCLIC COMPOUNDS; MICE; MOLECULAR STRUCTURE; PARASITIC DISEASES, ANIMAL; PARASITIC SENSITIVITY TESTS; PLASMODIUM YOELII; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 57349129495     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm801006v     Document Type: Article

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34. 13 Mice treated with β-arteether served as positive control.
35. (a) 100% suppression of parasitaemia means no parasites were detected in 50 oil immersion microscopic fields (parasites, if at all present, are below the detection limit). The parasites present below the detection limit can multiply and eventually can be detected during observation on subsequent days. In such cases though the drug is providing near 100% suppression of the parasitaemia on day 4, it will not provide full protection to the treated mice in the 28 day survival assay. Multi-drug resistant Plasmodium yoelii nigeriensis used in this study is resistant to chloroquine, mefloquine, and halofantrine.
36. (b) 100% protection means none of the treated mice developed patent infection during the 28-day observation period and hence recorded as cured. Similarly, 20% protection means only 1 out of 5 mice was cured.
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