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Novel benzyl phenyl sulfide derivatives as antibacterial agents against methicillin-resistant Staphylococcus aureus

The Journal of Antibiotics volume 73, pages 82–90 (2020)Cite this article

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Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major threat to human health due to its resistance to almost all classes of antibiotics. Discovery of novel antibacterial agents with new structures which combat the pathogens responsible for MRSA is urgent. In this study, three series of benzyl phenyl sulfide derivatives were designed and synthesized, and their antibacterial activity against eleven MRSA strains were evaluated. The results showed that two series of the synthetic compounds (5a-5l and 12p-12u) exhibit potent antibacterial activity against S. aureus and MRSA, with minimum inhibitory concentrations of 2–64 μg/mL. The structure-activity relationships are discussed and the mechanism of the antibacterial activity was shown to involve the destruction of the bacterial cell membrane. Finally, the MTT assay results suggest that the toxicity of compounds 5f and 5h is selective between bacteria and mammalian cells.

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Acknowledgements

We sincerely thank the National Natural Science Foundation of China (81673336), Pearl River S&T Nova Program of Guangzhou (201806010116), and the Fundamental Research Funds for the Central University (21617478) for financial support of this study. We sincerely thank Lingwei Wang and Yuemei Lu from the Second Clinical Medical College of Jinan University for their donation of clinical isolated MRSA strains.

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  1. These authors contributed equally: Kuo Lu, Qi Chen

Authors and Affiliations

  1. International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou, 510632, PR China

    Kuo Lu, Qi Chen, Xiao-Fang Xu, Ying Meng, Jing Lin & Wei-Min Chen

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  1. Kuo Lu
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  2. Qi Chen
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Correspondence to Jing Lin or Wei-Min Chen.

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Lu, K., Chen, Q., Xu, XF. et al. Novel benzyl phenyl sulfide derivatives as antibacterial agents against methicillin-resistant Staphylococcus aureus. J Antibiot 73, 82–90 (2020). https://doi.org/10.1038/s41429-019-0257-x

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