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The effect of novel β-lactam derivatives synthesized from substituted phenethylamines on resistance genes of MRSA isolates

The Journal of Antibiotics volume 77, pages 802–811 (2024)Cite this article

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Abstract

This study focuses on the activity of previously reported imine and β-lactam derivatives against methicillin-resistant Staphylococcus aureus (MRSA) isolates. The presence of mecA and blaZ genes in the isolates was determined, and the minimum inhibitory concentration (MIC) values were determined based on the antibacterial activity against these isolates. Active compounds were selected and their ability to act against resistant isolates in vitro was determined. Concurrently, biochemical (nitrocefin) and molecular (qRT-PCR) tests were used to investigate the ability of the compounds to induce resistance genes in MRSA isolates. The cytotoxicity of the compounds on human dermal fibroblasts (HDF) was investigated. The MIC values of compounds (10) and (12) against MSSA and MRSA isolates were 7.81 and 15.62 μg ml−1, respectively. The most active compounds were identified as (10) and (12), and it was observed that the isolates did not develop resistance to these compounds in vitro. These compounds were found to inhibit β-lactamase, reduce the expression of resistance genes, and exhibit reduced HDF cell toxicity in a dose-dependent manner. According to the findings of the study, it can be concluded that these compounds show promise as hits with an interesting mechanism of action for further chemical modifications to develop new MRSA inhibitors.

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Acknowledgements

This study was supported by Erzurum Technical University (Master’s Thesis Project, 2021/004) and is based on the MSc thesis of Merve Yıldırım. We would like to thank Erzurum Technical University and YUTAM (High Technology and Research Center) for their financial support and research conditions.

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Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, 25050, Turkey

    Merve Yildirim

  2. Department of Basic Sciences, Faculty of Science, Erzurum Technical University, Erzurum, 25050, Turkey

    Bunyamin Ozgeris

  3. Department of Biology, Faculty of Science, Dokuz Eylul University, Izmir, 35390, Turkey

    Arzu Gormez

Authors
  1. Merve Yildirim
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  2. Bunyamin Ozgeris
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  3. Arzu Gormez
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Contributions

MY performed the analyses and wrote the first draft of the manuscript. AG and BO supervised the study and interpreted the results. All authors contributed to the revision of the manuscript and have read and approved the submitted version.

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Correspondence to Arzu Gormez.

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Yildirim, M., Ozgeris, B. & Gormez, A. The effect of novel β-lactam derivatives synthesized from substituted phenethylamines on resistance genes of MRSA isolates. J Antibiot 77, 802–811 (2024). https://doi.org/10.1038/s41429-024-00769-5

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