Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents
The efficacy of most marketed antimalarial drugs has been compromised by the development of parasite resistance, underscoring an urgent need to find new drugs with new mechanisms of action. This article describes the synthesis and the in vitro antimalarial profiling of antifolate P218 analogues, by...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Journal of Saudi Chemical Society |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319610322001211 |
| _version_ | 1811293440233701376 |
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| author | Moaz M. Abdou Paul M. O'Neill Eric Amigues Magdalini Matziari |
| author_facet | Moaz M. Abdou Paul M. O'Neill Eric Amigues Magdalini Matziari |
| author_sort | Moaz M. Abdou |
| collection | DOAJ |
| description | The efficacy of most marketed antimalarial drugs has been compromised by the development of parasite resistance, underscoring an urgent need to find new drugs with new mechanisms of action. This article describes the synthesis and the in vitro antimalarial profiling of antifolate P218 analogues, by exploring a bioisosteric replacement of the carboxylic group by a phosphinic moiety as well as structural isomerization of P218. The detailed synthetic route employed to access the title compounds is described. The listed compounds exhibited low antimalarial activity against drug-resistant strains of P. falciparum including chloroquine-resistant W2. |
| first_indexed | 2024-04-13T05:01:25Z |
| format | Article |
| id | doaj.art-1f4e1c9472b5478daa5da507d6fb6f93 |
| institution | Directory Open Access Journal |
| issn | 1319-6103 |
| language | English |
| last_indexed | 2024-04-13T05:01:25Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj.art-1f4e1c9472b5478daa5da507d6fb6f932022-12-22T03:01:18ZengElsevierJournal of Saudi Chemical Society1319-61032022-11-01266101539Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agentsMoaz M. Abdou0Paul M. O'Neill1Eric Amigues2Magdalini Matziari3Egyptian Petroleum Research Institute, Nasr City, P.O. 11727, Cairo, Egypt; Corresponding authors.Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UKDepartment of Chemistry, Xi’an Jiaotong Liverpool University, Suzhou 215123, PR ChinaDepartment of Chemistry, Xi’an Jiaotong Liverpool University, Suzhou 215123, PR China; Corresponding authors.The efficacy of most marketed antimalarial drugs has been compromised by the development of parasite resistance, underscoring an urgent need to find new drugs with new mechanisms of action. This article describes the synthesis and the in vitro antimalarial profiling of antifolate P218 analogues, by exploring a bioisosteric replacement of the carboxylic group by a phosphinic moiety as well as structural isomerization of P218. The detailed synthetic route employed to access the title compounds is described. The listed compounds exhibited low antimalarial activity against drug-resistant strains of P. falciparum including chloroquine-resistant W2.http://www.sciencedirect.com/science/article/pii/S1319610322001211Antimalarial2,4-DiaminopyrimidinesPhosphinic acidP218BioisosterismMalarial dihydrofolate reductase |
| spellingShingle | Moaz M. Abdou Paul M. O'Neill Eric Amigues Magdalini Matziari Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents Journal of Saudi Chemical Society Antimalarial 2,4-Diaminopyrimidines Phosphinic acid P218 Bioisosterism Malarial dihydrofolate reductase |
| title | Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents |
| title_full | Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents |
| title_fullStr | Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents |
| title_full_unstemmed | Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents |
| title_short | Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents |
| title_sort | structure based bioisosteric design synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents |
| topic | Antimalarial 2,4-Diaminopyrimidines Phosphinic acid P218 Bioisosterism Malarial dihydrofolate reductase |
| url | http://www.sciencedirect.com/science/article/pii/S1319610322001211 |
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