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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 |
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author | Lum, Kah Yean White, Jonathan M Johnson, Daniel J G Avery, Vicky M Davis, Rohan A |
author_facet | Lum, Kah Yean White, Jonathan M Johnson, Daniel J G Avery, Vicky M Davis, Rohan A |
author_sort | Lum, Kah Yean |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9907012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Beilstein-Institut |
record_format | MEDLINE/PubMed |
spelling | pubmed-99070122023-02-08 Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds Lum, Kah Yean White, Jonathan M Johnson, Daniel J G Avery, Vicky M Davis, Rohan A Beilstein J Org Chem Full Research Paper 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. Beilstein-Institut 2023-01-31 /pmc/articles/PMC9907012/ /pubmed/36761470 http://dx.doi.org/10.3762/bjoc.19.11 Text en Copyright © 2023, Lum et al. https://creativecommons.org/licenses/by/4.0/This is an open access article licensed under the terms of the Beilstein-Institut Open Access License Agreement (https://www.beilstein-journals.org/bjoc/terms/terms), which is identical to the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ). The reuse of material under this license requires that the author(s), source and license are credited. Third-party material in this article could be subject to other licenses (typically indicated in the credit line), and in this case, users are required to obtain permission from the license holder to reuse the material. |
spellingShingle | Full Research Paper Lum, Kah Yean White, Jonathan M Johnson, Daniel J G Avery, Vicky M Davis, Rohan A Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds |
title | Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds |
title_full | Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds |
title_fullStr | Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds |
title_full_unstemmed | Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds |
title_short | Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds |
title_sort | synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds |
topic | Full Research Paper |
url | 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 |
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