Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode
Multi-drug resistant bacterial strains (MDR) have become an increasing challenge to our health system, resulting in multiple classical antibiotics being clinically inactive today. As the de-novo development of effective antibiotics is a very costly and time-consuming process, alternative strategies...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5319 |
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| author | Adam Burke Mara Di Filippo Silvia Spiccio Anna Maria Schito Debora Caviglia Chiara Brullo Marcus Baumann |
| author_facet | Adam Burke Mara Di Filippo Silvia Spiccio Anna Maria Schito Debora Caviglia Chiara Brullo Marcus Baumann |
| author_sort | Adam Burke |
| collection | DOAJ |
| description | Multi-drug resistant bacterial strains (MDR) have become an increasing challenge to our health system, resulting in multiple classical antibiotics being clinically inactive today. As the de-novo development of effective antibiotics is a very costly and time-consuming process, alternative strategies such as the screening of natural and synthetic compound libraries is a simple approach towards finding new lead compounds. We thus report on the antimicrobial evaluation of a small collection of fourteen drug-like compounds featuring indazoles, pyrazoles and pyrazolines as key heterocyclic moieties whose synthesis was achieved in continuous flow mode. It was found that several compounds possessed significant antibacterial potency against clinical and MDR strains of the <i>Staphylococcus</i> and <i>Enterococcus</i> genera, with the lead compound (<b>9</b>) reaching MIC values of 4 µg/mL on those species. In addition, time killing experiments performed on compound <b>9</b> on <i>Staphylococcus aureus</i> MDR strains highlight its activity as bacteriostatic. Additional evaluations regarding the physiochemical and pharmacokinetic properties of the most active compounds are reported and showcased, promising drug-likeness, which warrants further explorations of the newly identified antimicrobial lead compound. |
| first_indexed | 2024-03-11T06:26:50Z |
| format | Article |
| id | doaj.art-30027e907bc54b93921dda19568539eb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:50Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-30027e907bc54b93921dda19568539eb2023-11-17T11:32:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246531910.3390/ijms24065319Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow ModeAdam Burke0Mara Di Filippo1Silvia Spiccio2Anna Maria Schito3Debora Caviglia4Chiara Brullo5Marcus Baumann6Science Centre South, School of Chemistry, University College Dublin, Dublin 4, IrelandScience Centre South, School of Chemistry, University College Dublin, Dublin 4, IrelandScience Centre South, School of Chemistry, University College Dublin, Dublin 4, IrelandDepartment of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genoa, ItalyDepartment of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genoa, ItalySection of Medicinal Chemistry, Department of Pharmacy (DIFAR), University of Genoa, 16132 Genoa, ItalyScience Centre South, School of Chemistry, University College Dublin, Dublin 4, IrelandMulti-drug resistant bacterial strains (MDR) have become an increasing challenge to our health system, resulting in multiple classical antibiotics being clinically inactive today. As the de-novo development of effective antibiotics is a very costly and time-consuming process, alternative strategies such as the screening of natural and synthetic compound libraries is a simple approach towards finding new lead compounds. We thus report on the antimicrobial evaluation of a small collection of fourteen drug-like compounds featuring indazoles, pyrazoles and pyrazolines as key heterocyclic moieties whose synthesis was achieved in continuous flow mode. It was found that several compounds possessed significant antibacterial potency against clinical and MDR strains of the <i>Staphylococcus</i> and <i>Enterococcus</i> genera, with the lead compound (<b>9</b>) reaching MIC values of 4 µg/mL on those species. In addition, time killing experiments performed on compound <b>9</b> on <i>Staphylococcus aureus</i> MDR strains highlight its activity as bacteriostatic. Additional evaluations regarding the physiochemical and pharmacokinetic properties of the most active compounds are reported and showcased, promising drug-likeness, which warrants further explorations of the newly identified antimicrobial lead compound.https://www.mdpi.com/1422-0067/24/6/5319pyrazoleindazolepyrazolineflow chemistryantibacterial agentsantibiotic resistance |
| spellingShingle | Adam Burke Mara Di Filippo Silvia Spiccio Anna Maria Schito Debora Caviglia Chiara Brullo Marcus Baumann Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode International Journal of Molecular Sciences pyrazole indazole pyrazoline flow chemistry antibacterial agents antibiotic resistance |
| title | Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode |
| title_full | Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode |
| title_fullStr | Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode |
| title_full_unstemmed | Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode |
| title_short | Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode |
| title_sort | antimicrobial evaluation of new pyrazoles indazoles and pyrazolines prepared in continuous flow mode |
| topic | pyrazole indazole pyrazoline flow chemistry antibacterial agents antibiotic resistance |
| url | https://www.mdpi.com/1422-0067/24/6/5319 |
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