Pyrazolo[1,5-a]pyrimidin-7-ones as promising antimicrobial scaffolds: In vitro and in vivo evaluation.
This study presents a family of pyrazolo[1,5-a]pyrimidin-7-ones as potential antimicrobial agents. Initial screening against Staphylococcus aureus, Escherichia coli, and Candida albicans identified compound 3 as active against S. aureus (MIC₅₀ 1.8 μM). A structure activity relationship study of 35 a...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625003868 |
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| author | Amanda A. Doyle Mark Kelada Clara Charleton Robert Devine John M.D. Walsh Ronan Bergin Kevin Kavanagh John C. Stephens |
| author_facet | Amanda A. Doyle Mark Kelada Clara Charleton Robert Devine John M.D. Walsh Ronan Bergin Kevin Kavanagh John C. Stephens |
| author_sort | Amanda A. Doyle |
| collection | DOAJ |
| description | This study presents a family of pyrazolo[1,5-a]pyrimidin-7-ones as potential antimicrobial agents. Initial screening against Staphylococcus aureus, Escherichia coli, and Candida albicans identified compound 3 as active against S. aureus (MIC₅₀ 1.8 μM). A structure activity relationship study of 35 analogues yielded the more potent analogues (MIC₅₀ 1.2 μM, MIC₈₀ 6.4 μM). Hit compounds were further evaluated against Methicillin-Resistant S. aureus (MRSA) and Pseudomonas aeruginosa, with pyrimidinone 12 showing the strongest activity against MRSA (MIC₅₀ 1.88 μM, MIC₈₀ 2.93 μM). In vivo toxicity assessment using Galleria mellonella larvae indicated that the leading active compounds were non-toxic. Importantly, in an in vivo G. Melonella MRSA infection model, compound 12 improved survival by 25 % compared to untreated controls (95 % vs. 75 %, p < 0.05). These strong in vivo results highlight pyrazolo[1,5-a]pyrimidin-7-ones as promising scaffolds for the development of new antibacterial agents. |
| format | Article |
| id | doaj-art-6bd263dee2d04a64b8687138a3be4c0c |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-6bd263dee2d04a64b8687138a3be4c0c2025-08-20T03:43:47ZengElsevierResults in Chemistry2211-71562025-07-011610240310.1016/j.rechem.2025.102403Pyrazolo[1,5-a]pyrimidin-7-ones as promising antimicrobial scaffolds: In vitro and in vivo evaluation.Amanda A. Doyle0Mark Kelada1Clara Charleton2Robert Devine3John M.D. Walsh4Ronan Bergin5Kevin Kavanagh6John C. Stephens7Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, IrelandDepartment of Chemistry, Maynooth University, Maynooth, Co. Kildare, IrelandDepartment of Chemistry, Maynooth University, Maynooth, Co. Kildare, IrelandDepartment of Chemistry, Maynooth University, Maynooth, Co. Kildare, IrelandDepartment of Chemistry, Maynooth University, Maynooth, Co. Kildare, IrelandDepartment of Biology, Maynooth University, Maynooth, Co. Kildare, IrelandDepartment of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland; The Kathleen Lonsdale Institute of Human Health Research, Maynooth University, Maynooth, Co. Kildare, IrelandDepartment of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland; The Kathleen Lonsdale Institute of Human Health Research, Maynooth University, Maynooth, Co. Kildare, Ireland; Corresponding author at: Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland.This study presents a family of pyrazolo[1,5-a]pyrimidin-7-ones as potential antimicrobial agents. Initial screening against Staphylococcus aureus, Escherichia coli, and Candida albicans identified compound 3 as active against S. aureus (MIC₅₀ 1.8 μM). A structure activity relationship study of 35 analogues yielded the more potent analogues (MIC₅₀ 1.2 μM, MIC₈₀ 6.4 μM). Hit compounds were further evaluated against Methicillin-Resistant S. aureus (MRSA) and Pseudomonas aeruginosa, with pyrimidinone 12 showing the strongest activity against MRSA (MIC₅₀ 1.88 μM, MIC₈₀ 2.93 μM). In vivo toxicity assessment using Galleria mellonella larvae indicated that the leading active compounds were non-toxic. Importantly, in an in vivo G. Melonella MRSA infection model, compound 12 improved survival by 25 % compared to untreated controls (95 % vs. 75 %, p < 0.05). These strong in vivo results highlight pyrazolo[1,5-a]pyrimidin-7-ones as promising scaffolds for the development of new antibacterial agents.http://www.sciencedirect.com/science/article/pii/S2211715625003868Antimicrobial activityAnti-MRSA agentsSAR study |
| spellingShingle | Amanda A. Doyle Mark Kelada Clara Charleton Robert Devine John M.D. Walsh Ronan Bergin Kevin Kavanagh John C. Stephens Pyrazolo[1,5-a]pyrimidin-7-ones as promising antimicrobial scaffolds: In vitro and in vivo evaluation. Results in Chemistry Antimicrobial activity Anti-MRSA agents SAR study |
| title | Pyrazolo[1,5-a]pyrimidin-7-ones as promising antimicrobial scaffolds: In vitro and in vivo evaluation. |
| title_full | Pyrazolo[1,5-a]pyrimidin-7-ones as promising antimicrobial scaffolds: In vitro and in vivo evaluation. |
| title_fullStr | Pyrazolo[1,5-a]pyrimidin-7-ones as promising antimicrobial scaffolds: In vitro and in vivo evaluation. |
| title_full_unstemmed | Pyrazolo[1,5-a]pyrimidin-7-ones as promising antimicrobial scaffolds: In vitro and in vivo evaluation. |
| title_short | Pyrazolo[1,5-a]pyrimidin-7-ones as promising antimicrobial scaffolds: In vitro and in vivo evaluation. |
| title_sort | pyrazolo 1 5 a pyrimidin 7 ones as promising antimicrobial scaffolds in vitro and in vivo evaluation |
| topic | Antimicrobial activity Anti-MRSA agents SAR study |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625003868 |
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