Synthesis of 1-(2-Hydroxy-5-methylphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives as a Promising Scaffold Against Disease-Causing Bacteria Relevant to Public Health
The increasing number of antibiotic-resistant pathogens forces us to accelerate the search for new antimicrobial agents. Based on this, we chose to synthesize a library of 1-(2-hydroxy-5-methylphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives and evaluate their antibacterial activity against va...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/12/2639 |
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| Summary: | The increasing number of antibiotic-resistant pathogens forces us to accelerate the search for new antimicrobial agents. Based on this, we chose to synthesize a library of 1-(2-hydroxy-5-methylphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives and evaluate their antibacterial activity against various pathogens. A series of (2-hydroxy-5-methylphenyl)-5-oxopyrrolidine-3-carboxylic acid and its hydrazide derivatives were prepared and identified by the methods of IR, <sup>1</sup>H, and <sup>13</sup>C NMR spectroscopy and a microanalysis technique. The resulting compounds were evaluated in vitro for their efficacy against the Gram-positive <i>Staphylococcus aureus</i> (ATCC 9144), <i>Listeria monocytogenes</i> (ATCC 7644), and <i>Bacillus cereus</i> (ATCC 11778) bacterial strains as well as the Gram-negative <i>Escherichia coli</i> (ATCC 8739) bacteria. Oxacillin, ampicillin, and cefuroxime were used as control antibiotics. Among the obtained compounds, hydrazone with a 5-nitrothien-2-yl fragment surpassed the control cefuroxime (7.8 μg/mL) against almost all strains tested. Hydrazone with a 5-nitrofuran-2-yl moiety showed a slightly lower but also potent effect on all bacterial strains. Moreover, hydrazone with a benzylidene moiety demonstrated very strong inhibition of <i>S. aureus</i> (3.9 μg/mL) in comparison with the antibacterial drug cefuroxime (7.8 μg/mL). In addition, some of these compounds exhibited remarkable bactericidal properties. In a complete biofilm disruption study, 5-nitrothienylhydrazone showed excellent results in disrupting <i>S. aureus</i> and <i>E. coli</i> biofilms. The test results show the potential of the newly obtained derivatives as a source of antibacterial agents. Therefore, further studies on the molecular optimization of these compounds are necessary for the development of new antibacterial drugs. |
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| ISSN: | 1420-3049 |