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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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2023-01-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.19.11 |
| _version_ | 1811170098659983360 |
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| author | Kah Yean Lum Jonathan M. White Daniel J. G. Johnson Vicky M. Avery Rohan A. Davis |
| author_facet | Kah Yean Lum Jonathan M. White Daniel J. G. Johnson Vicky M. Avery Rohan A. Davis |
| author_sort | Kah Yean Lum |
| collection | DOAJ |
| 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 IC50 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 CF3 and CF2H moieties, whereas incorporation of a CF2Me group at the same position completely abolished antiplasmodial effects. |
| first_indexed | 2024-04-10T16:52:55Z |
| format | Article |
| id | doaj.art-47b1a25598904fc99698afc06978edcb |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-04-10T16:52:55Z |
| publishDate | 2023-01-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-47b1a25598904fc99698afc06978edcb2023-02-07T10:59:15ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972023-01-0119110711410.3762/bjoc.19.111860-5397-19-11Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compoundsKah Yean Lum0Jonathan M. White1Daniel J. G. Johnson2Vicky M. Avery3Rohan A. Davis4Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Nathan, QLD 4111, Australia School of Chemistry and Bio21 Institute, The University of Melbourne, Melbourne, VIC 3010, Australia Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Nathan, QLD 4111, Australia Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Nathan, QLD 4111, Australia Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Nathan, QLD 4111, Australia 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 IC50 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 CF3 and CF2H moieties, whereas incorporation of a CF2Me group at the same position completely abolished antiplasmodial effects.https://doi.org/10.3762/bjoc.19.11antimalarialcharacterisationdiversinatetmfluorinetriazolopyrazinescaffoldopen source malaria |
| spellingShingle | Kah Yean Lum Jonathan M. White Daniel J. G. Johnson Vicky M. Avery Rohan A. Davis Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds Beilstein Journal of Organic Chemistry antimalarial characterisation diversinatetm fluorine triazolopyrazine scaffold open source malaria |
| 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 | antimalarial characterisation diversinatetm fluorine triazolopyrazine scaffold open source malaria |
| url | https://doi.org/10.3762/bjoc.19.11 |
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