Orally active esters of dihydroartemisinin: Synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in mice

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 4, 2008, Pages 1436-1441

  Singh, Chandan ^a   Chaudhary, Sandeep ^a   Puri, Sunil K ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

Author keywords

1,2,4 Trioxanes; Antimalarial; Arteether; Dihydroartemisinin; Multidrug resistant

Indexed keywords

ARTEETHER; ARTESUNATE; DIHYDROARTEMISININ; DIHYDROARTEMISININ DERIVATIVE; ESTER DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBIOTIC RESISTANCE; ANTIMALARIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG SCREENING; EXPERIMENTAL MOUSE; MALARIA; MALE; MOUSE; NONHUMAN; PLASMODIUM YOELII; PROTECTION; STRUCTURE ACTIVITY RELATION;

ADAMANTANE; ADMINISTRATION, ORAL; ANIMALS; ANTIMALARIALS; ARTEMISININS; BIPHENYL COMPOUNDS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, MULTIPLE; ESTERS; MALARIA; MICE; MODELS, MOLECULAR; PLASMODIUM YOELII; SESQUITERPENES; STRUCTURE-ACTIVITY RELATIONSHIP;

MUS; PLASMODIUM YOELII; PLASMODIUM YOELII NIGERIENSIS;

EID: 39049132961     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.12.074     Document Type: Article

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31. 100% suppression of parasitamia means no parasites were detected in 50 oil immersion microscopic fields (parasites if at all present were 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.
32. 100% protection means none of the treated mice developed patent infection during the 28 days observation period and hence were recorded as cured. Similarly 60% protection means only 3 out of 5 mice were cured.
33. Energy minimized three-dimensional structures were generated using Builder (Insight II) module.
34. Following a suggestion from one of the reviewers, we compared the stabilities of artemether 3 and ester 7i under acidic conditions (1:1 mixture of THF and 10% aqueous HCl). While artemether was completely degraded within 96 h, 80% of the ester 7i was recovered unchanged under the same conditions.
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