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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Beilstein-Institut
2023
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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 |
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. |
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