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Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

Nine new fluorinated analogues were synthesised by late-stage functionalisation using Diversinate™ chemistry on the Open Source Malaria (OSM) triazolopyrazine scaffold (Series 4). The structures of all analogues were fully characterised by NMR, UV and MS data analysis; three triazolopyrazines were c...

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Detalles Bibliográficos
Autores principales: Lum, Kah Yean, White, Jonathan M, Johnson, Daniel J G, Avery, Vicky M, Davis, Rohan A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907012/
https://www.ncbi.nlm.nih.gov/pubmed/36761470
http://dx.doi.org/10.3762/bjoc.19.11
Descripción
Sumario:Nine new fluorinated analogues were synthesised by late-stage functionalisation using Diversinate™ chemistry on the Open Source Malaria (OSM) triazolopyrazine scaffold (Series 4). The structures of all analogues were fully characterised by NMR, UV and MS data analysis; three triazolopyrazines were confirmed by X-ray crystal structure analysis. The inhibitory activity of all compounds against the growth of the malaria parasite Plasmodium falciparum (3D7 and Dd2 strains) and the cytotoxicity against a human embryonic kidney (HEK293) cell line were tested. Some of the compounds demonstrated moderate antimalarial activity with IC(50) values ranging from 0.2 to >80 µM; none of the compounds displayed any cytotoxicity against HEK293 cells at 80 µM. Antimalarial activity was significantly reduced when C-8 of the triazolopyrazine scaffold was substituted with CF(3) and CF(2)H moieties, whereas incorporation of a CF(2)Me group at the same position completely abolished antiplasmodial effects.