Synthesis of New Triazolopyrazine Antimalarial Compounds
A radical approach to late-stage functionalization using photoredox and Diversinate<sup>™</sup> chemistry on the Open Source Malaria (OSM) triazolopyrazine scaffold (Series 4) resulted in the synthesis of 12 new analogues, which were characterized by NMR, UV, and MS data analysis. The st...
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MDPI AG
2021-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/9/2421 |
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doaj-6f3deda7a0494610ab87f1141ddbc3842021-04-21T23:06:15ZengMDPI AGMolecules1420-30492021-04-01262421242110.3390/molecules26092421Synthesis of New Triazolopyrazine Antimalarial CompoundsDaniel J. G. Johnson0Ian D. Jenkins1Cohan Huxley2Mark J. Coster3Kah Yean Lum4Jonathan M. White5Vicky M. Avery6Rohan A. Davis7Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, AustraliaGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, AustraliaGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, AustraliaGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, AustraliaGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, AustraliaSchool of Chemistry and Bio21 Institute, The University of Melbourne, Melbourne, VIC 3010, AustraliaGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, AustraliaGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, AustraliaA radical approach to late-stage functionalization using photoredox and Diversinate<sup>™</sup> chemistry on the Open Source Malaria (OSM) triazolopyrazine scaffold (Series 4) resulted in the synthesis of 12 new analogues, which were characterized by NMR, UV, and MS data analysis. The structures of four triazolopyrazines were confirmed by X-ray crystal structure analysis. Several minor and unexpected side products were generated during these studies, including two resulting from a possible disproportionation reaction. All compounds were tested for their ability to inhibit the growth of the malaria parasite <i>Plasmodium falciparum</i> (3D7 and Dd2 strains) and for cytotoxicity against a human embryonic kidney (HEK293) cell line. Moderate antimalarial activity was observed for some of the compounds, with IC<sub>50</sub> values ranging from 0.3 to >20 µM; none of the compounds displayed any toxicity against HEK293 at 80 µM.https://www.mdpi.com/1420-3049/26/9/2421Open Source Malariadrug discoverysynthesistriazolopyrazinelate-stage functionalizationphotoredox |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Daniel J. G. Johnson Ian D. Jenkins Cohan Huxley Mark J. Coster Kah Yean Lum Jonathan M. White Vicky M. Avery Rohan A. Davis |
| spellingShingle |
Daniel J. G. Johnson Ian D. Jenkins Cohan Huxley Mark J. Coster Kah Yean Lum Jonathan M. White Vicky M. Avery Rohan A. Davis Synthesis of New Triazolopyrazine Antimalarial Compounds Molecules Open Source Malaria drug discovery synthesis triazolopyrazine late-stage functionalization photoredox |
| author_facet |
Daniel J. G. Johnson Ian D. Jenkins Cohan Huxley Mark J. Coster Kah Yean Lum Jonathan M. White Vicky M. Avery Rohan A. Davis |
| author_sort |
Daniel J. G. Johnson |
| title |
Synthesis of New Triazolopyrazine Antimalarial Compounds |
| title_short |
Synthesis of New Triazolopyrazine Antimalarial Compounds |
| title_full |
Synthesis of New Triazolopyrazine Antimalarial Compounds |
| title_fullStr |
Synthesis of New Triazolopyrazine Antimalarial Compounds |
| title_full_unstemmed |
Synthesis of New Triazolopyrazine Antimalarial Compounds |
| title_sort |
synthesis of new triazolopyrazine antimalarial compounds |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2021-04-01 |
| description |
A radical approach to late-stage functionalization using photoredox and Diversinate<sup>™</sup> chemistry on the Open Source Malaria (OSM) triazolopyrazine scaffold (Series 4) resulted in the synthesis of 12 new analogues, which were characterized by NMR, UV, and MS data analysis. The structures of four triazolopyrazines were confirmed by X-ray crystal structure analysis. Several minor and unexpected side products were generated during these studies, including two resulting from a possible disproportionation reaction. All compounds were tested for their ability to inhibit the growth of the malaria parasite <i>Plasmodium falciparum</i> (3D7 and Dd2 strains) and for cytotoxicity against a human embryonic kidney (HEK293) cell line. Moderate antimalarial activity was observed for some of the compounds, with IC<sub>50</sub> values ranging from 0.3 to >20 µM; none of the compounds displayed any toxicity against HEK293 at 80 µM. |
| topic |
Open Source Malaria drug discovery synthesis triazolopyrazine late-stage functionalization photoredox |
| url |
https://www.mdpi.com/1420-3049/26/9/2421 |
| work_keys_str_mv |
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1721515350258876416 |