Linked Life Data

11911834

Source:http://linkedlifedata.com/resource/pubmed/id/11911834

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-3-25
pubmed:abstractText
We report the synthesis of a series of novel phenothiazine compounds that inhibit the growth of both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. We found that the antimalarial activity of these phenothiazines increased with an increase in the number of basic groups in the alkylamino side chain, which may reflect increased uptake into the parasite food vacuole or differences in the toxicities of individual FP-drug complexes. We have examined the ability of the parent phenothiazine, chlorpromazine, and some novel phenothiazines to inhibit the formation of beta-haematin. The degree of antimalarial potency was loosely correlated with the efficacy of inhibition of beta-haematin formation, suggesting that these phenothiazines exert their antimalarial activities in a manner similar to that of chloroquine, i.e. by antagonizing the sequestration of toxic haem (ferriprotoporphyrin IX) moieties within the malaria parasite. Chlorpromazine is an effective modulator of chloroquine resistance; however, the more potent phenothiazine derivatives were more active against chloroquine-sensitive parasites than against chloroquine-resistant parasites and showed little synergy of action when used in combination with chloroquine. These studies point to structural features that may determine the antimalarial activity and resistance modulating potential of weakly basic amphipaths.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
833-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Novel phenothiazine antimalarials: synthesis, antimalarial activity, and inhibition of the formation of beta-haematin.
pubmed:affiliation
Department of Chemistry, La Trobe University, 3086, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't