Cargando…

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...

Descripción completa

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
_version_ 1784884085047427072
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
work_keys_str_mv AT lumkahyean synthesisandcharacterisationofnewantimalarialfluorinatedtriazolopyrazinecompounds
AT whitejonathanm synthesisandcharacterisationofnewantimalarialfluorinatedtriazolopyrazinecompounds
AT johnsondanieljg synthesisandcharacterisationofnewantimalarialfluorinatedtriazolopyrazinecompounds
AT averyvickym synthesisandcharacterisationofnewantimalarialfluorinatedtriazolopyrazinecompounds
AT davisrohana synthesisandcharacterisationofnewantimalarialfluorinatedtriazolopyrazinecompounds