Matches in SemOpenAlex for { <https://semopenalex.org/work/W2145095908> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W2145095908 endingPage "428" @default.
- W2145095908 startingPage "428" @default.
- W2145095908 abstract "<h3>Abstract</h3> Malaria eradication requires the development of new drugs to combat drug-resistant parasites. The search for new chemical scaffolds that target novel pathways of the human malaria parasite <i>Plasmodium falciparum</i> is of highest priority. We identified bisbenzylisoquinoline alkaloids isolated from <i>Cocculus hirsutus</i>. (trilobine derivatives) as active in the nanomolar range against <i>P. falciparum</i> blood stages. Synthesis of a library of 94 hemi-synthetic derivatives allowed us to identify compound <b>84</b> that kills multi-drug resistant clinical isolates in the nanomolar range (median IC<sub>50</sub> ranging from 35-88nM). Efforts were made to obtain compounds with significantly improved preclinical properties. Out of those, compound <b>125</b> delays the onset of parasitemia in <i>P. berghei</i> infected mice and inhibits <i>P. falciparum</i> transmission stages <i>in vitro</i> (culture assays) and <i>in vivo</i> using membrane feeding assay in the <i>Anopheles stephensi</i> vector. Compound <b>125</b> also impairs <i>P. falciparum</i> development in sporozoite-infected hepatocytes, in the low micromolar range. Finally, we used a chemical pull-down strategy to identify potential protein targets of this chemical family. Mass spectrometry analysis identified the parasite interactome with trilobine derivatives, identifying protein partners belonging to metabolic pathways that have not been previously targeted by antimalarial drugs or implicated in drug-resistance mechanisms." @default.
- W2145095908 created "2016-06-24" @default.
- W2145095908 creator A5091678274 @default.
- W2145095908 date "2006-04-01" @default.
- W2145095908 modified "2023-09-27" @default.
- W2145095908 title "Presurgical evaluations of patients with intractable epilepsy" @default.
- W2145095908 cites W2093569051 @default.
- W2145095908 cites W2133396632 @default.
- W2145095908 cites W2137619660 @default.
- W2145095908 cites W2157538357 @default.
- W2145095908 doi "https://doi.org/10.1136/jnnp.2005.085423" @default.
- W2145095908 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2077496" @default.
- W2145095908 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16543518" @default.
- W2145095908 hasPublicationYear "2006" @default.
- W2145095908 type Work @default.
- W2145095908 sameAs 2145095908 @default.
- W2145095908 citedByCount "0" @default.
- W2145095908 crossrefType "journal-article" @default.
- W2145095908 hasAuthorship W2145095908A5091678274 @default.
- W2145095908 hasBestOaLocation W21450959082 @default.
- W2145095908 hasConcept C114851261 @default.
- W2145095908 hasConcept C136764020 @default.
- W2145095908 hasConcept C173758957 @default.
- W2145095908 hasConcept C185592680 @default.
- W2145095908 hasConcept C202751555 @default.
- W2145095908 hasConcept C203014093 @default.
- W2145095908 hasConcept C207001950 @default.
- W2145095908 hasConcept C2775867548 @default.
- W2145095908 hasConcept C2777775583 @default.
- W2145095908 hasConcept C2778048844 @default.
- W2145095908 hasConcept C2778371730 @default.
- W2145095908 hasConcept C2780035454 @default.
- W2145095908 hasConcept C2780478335 @default.
- W2145095908 hasConcept C41008148 @default.
- W2145095908 hasConcept C54355233 @default.
- W2145095908 hasConcept C55493867 @default.
- W2145095908 hasConcept C59822182 @default.
- W2145095908 hasConcept C64903051 @default.
- W2145095908 hasConcept C71928629 @default.
- W2145095908 hasConcept C74187038 @default.
- W2145095908 hasConcept C86803240 @default.
- W2145095908 hasConcept C89423630 @default.
- W2145095908 hasConcept C98274493 @default.
- W2145095908 hasConceptScore W2145095908C114851261 @default.
- W2145095908 hasConceptScore W2145095908C136764020 @default.
- W2145095908 hasConceptScore W2145095908C173758957 @default.
- W2145095908 hasConceptScore W2145095908C185592680 @default.
- W2145095908 hasConceptScore W2145095908C202751555 @default.
- W2145095908 hasConceptScore W2145095908C203014093 @default.
- W2145095908 hasConceptScore W2145095908C207001950 @default.
- W2145095908 hasConceptScore W2145095908C2775867548 @default.
- W2145095908 hasConceptScore W2145095908C2777775583 @default.
- W2145095908 hasConceptScore W2145095908C2778048844 @default.
- W2145095908 hasConceptScore W2145095908C2778371730 @default.
- W2145095908 hasConceptScore W2145095908C2780035454 @default.
- W2145095908 hasConceptScore W2145095908C2780478335 @default.
- W2145095908 hasConceptScore W2145095908C41008148 @default.
- W2145095908 hasConceptScore W2145095908C54355233 @default.
- W2145095908 hasConceptScore W2145095908C55493867 @default.
- W2145095908 hasConceptScore W2145095908C59822182 @default.
- W2145095908 hasConceptScore W2145095908C64903051 @default.
- W2145095908 hasConceptScore W2145095908C71928629 @default.
- W2145095908 hasConceptScore W2145095908C74187038 @default.
- W2145095908 hasConceptScore W2145095908C86803240 @default.
- W2145095908 hasConceptScore W2145095908C89423630 @default.
- W2145095908 hasConceptScore W2145095908C98274493 @default.
- W2145095908 hasIssue "4" @default.
- W2145095908 hasLocation W21450959081 @default.
- W2145095908 hasLocation W21450959082 @default.
- W2145095908 hasLocation W21450959083 @default.
- W2145095908 hasLocation W21450959084 @default.
- W2145095908 hasOpenAccess W2145095908 @default.
- W2145095908 hasPrimaryLocation W21450959081 @default.
- W2145095908 hasRelatedWork W1964955161 @default.
- W2145095908 hasRelatedWork W2002651169 @default.
- W2145095908 hasRelatedWork W2046040444 @default.
- W2145095908 hasRelatedWork W2114399685 @default.
- W2145095908 hasRelatedWork W2117123380 @default.
- W2145095908 hasRelatedWork W2121172260 @default.
- W2145095908 hasRelatedWork W2133748715 @default.
- W2145095908 hasRelatedWork W2355845593 @default.
- W2145095908 hasRelatedWork W2778565363 @default.
- W2145095908 hasRelatedWork W321717056 @default.
- W2145095908 hasVolume "77" @default.
- W2145095908 isParatext "false" @default.
- W2145095908 isRetracted "false" @default.
- W2145095908 magId "2145095908" @default.
- W2145095908 workType "article" @default.