Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds.
Kah Yean LumJonathan M WhiteDaniel J G JohnsonVicky Marie AveryRohan A DavisPublished in: Beilstein journal of organic chemistry (2023)
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.
Keyphrases
- plasmodium falciparum
- data analysis
- cystic fibrosis
- crystal structure
- high resolution
- molecular docking
- endothelial cells
- induced apoptosis
- magnetic resonance
- mass spectrometry
- multiple sclerosis
- ms ms
- computed tomography
- cell cycle arrest
- signaling pathway
- high intensity
- magnetic resonance imaging
- solid state
- dual energy
- molecular dynamics simulations