FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2135983047> ?p ?o ?g. }

• W2135983047 abstract "Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile.Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis.The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that were differentially expressed as a result of the treatment and gene ontology analysis identified various biological processes and molecular functions that were significantly affected. Comparison of the dehydrobrachylaenolide treatment transcriptional dataset with a published artesunate (also a sesquiterpene lactone) dataset revealed little overlap. These results strengthen the notion that the isolated compound and the artemisinins have differentiated modes of action.The novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts." @default.
• W2135983047 created "2016-06-24" @default.
• W2135983047 creator A5013508569 @default.
• W2135983047 creator A5035987292 @default.
• W2135983047 creator A5039869724 @default.
• W2135983047 creator A5050708098 @default.
• W2135983047 creator A5052192433 @default.
• W2135983047 creator A5058490973 @default.
• W2135983047 creator A5062876619 @default.
• W2135983047 creator A5067598836 @default.
• W2135983047 creator A5074337214 @default.
• W2135983047 creator A5085553882 @default.
• W2135983047 creator A5086881325 @default.
• W2135983047 creator A5058601249 @default.
• W2135983047 date "2011-10-11" @default.
• W2135983047 modified "2023-10-15" @default.
• W2135983047 title "In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling" @default.
• W2135983047 cites W1807878700 @default.
• W2135983047 cites W1966682505 @default.
• W2135983047 cites W1969503178 @default.
• W2135983047 cites W1977681293 @default.
• W2135983047 cites W1978098556 @default.
• W2135983047 cites W1981382039 @default.
• W2135983047 cites W1983323979 @default.
• W2135983047 cites W1986315098 @default.
• W2135983047 cites W1987619285 @default.
• W2135983047 cites W1991297121 @default.
• W2135983047 cites W1992051226 @default.
• W2135983047 cites W2010387696 @default.
• W2135983047 cites W2015620110 @default.
• W2135983047 cites W2018787119 @default.
• W2135983047 cites W2020251171 @default.
• W2135983047 cites W2029309961 @default.
• W2135983047 cites W2046961203 @default.
• W2135983047 cites W2050572265 @default.
• W2135983047 cites W2052236994 @default.
• W2135983047 cites W2061698805 @default.
• W2135983047 cites W2062914739 @default.
• W2135983047 cites W2069307360 @default.
• W2135983047 cites W2075101141 @default.
• W2135983047 cites W2077489556 @default.
• W2135983047 cites W2086140385 @default.
• W2135983047 cites W2098184601 @default.
• W2135983047 cites W2103740237 @default.
• W2135983047 cites W2108139198 @default.
• W2135983047 cites W2108244474 @default.
• W2135983047 cites W2112099544 @default.
• W2135983047 cites W2114918609 @default.
• W2135983047 cites W2115821311 @default.
• W2135983047 cites W2125397010 @default.
• W2135983047 cites W2144958373 @default.
• W2135983047 cites W2149548143 @default.
• W2135983047 cites W2161311583 @default.
• W2135983047 cites W2168317657 @default.
• W2135983047 cites W2296263363 @default.
• W2135983047 cites W4240125961 @default.
• W2135983047 doi "https://doi.org/10.1186/1475-2875-10-295" @default.
• W2135983047 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3200184" @default.
• W2135983047 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21985233" @default.
• W2135983047 hasPublicationYear "2011" @default.
• W2135983047 type Work @default.
• W2135983047 sameAs 2135983047 @default.
• W2135983047 citedByCount "40" @default.
• W2135983047 countsByYear W21359830472012 @default.
• W2135983047 countsByYear W21359830472013 @default.
• W2135983047 countsByYear W21359830472014 @default.
• W2135983047 countsByYear W21359830472015 @default.
• W2135983047 countsByYear W21359830472016 @default.
• W2135983047 countsByYear W21359830472017 @default.
• W2135983047 countsByYear W21359830472018 @default.
• W2135983047 countsByYear W21359830472019 @default.
• W2135983047 countsByYear W21359830472020 @default.
• W2135983047 countsByYear W21359830472021 @default.
• W2135983047 countsByYear W21359830472022 @default.
• W2135983047 countsByYear W21359830472023 @default.
• W2135983047 crossrefType "journal-article" @default.
• W2135983047 hasAuthorship W2135983047A5013508569 @default.
• W2135983047 hasAuthorship W2135983047A5035987292 @default.
• W2135983047 hasAuthorship W2135983047A5039869724 @default.
• W2135983047 hasAuthorship W2135983047A5050708098 @default.
• W2135983047 hasAuthorship W2135983047A5052192433 @default.
• W2135983047 hasAuthorship W2135983047A5058490973 @default.
• W2135983047 hasAuthorship W2135983047A5058601249 @default.
• W2135983047 hasAuthorship W2135983047A5062876619 @default.
• W2135983047 hasAuthorship W2135983047A5067598836 @default.
• W2135983047 hasAuthorship W2135983047A5074337214 @default.
• W2135983047 hasAuthorship W2135983047A5085553882 @default.
• W2135983047 hasAuthorship W2135983047A5086881325 @default.
• W2135983047 hasBestOaLocation W21359830471 @default.
• W2135983047 hasConcept C185592680 @default.
• W2135983047 hasConcept C195475562 @default.
• W2135983047 hasConcept C203014093 @default.
• W2135983047 hasConcept C2778048844 @default.
• W2135983047 hasConcept C2778371730 @default.
• W2135983047 hasConcept C55493867 @default.
• W2135983047 hasConcept C556039675 @default.
• W2135983047 hasConcept C71240020 @default.
• W2135983047 hasConcept C71924100 @default.
• W2135983047 hasConcept C86803240 @default.
• W2135983047 hasConceptScore W2135983047C185592680 @default.

• next