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Design, synthesis and biological evaluation of novel flavone Mannich base derivatives as potential antibacterial agents

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Abstract

A series of novel Mannich base derivatives of flavone containing benzylamine moiety was synthesized using the Mannich reaction. The results of antifungal activity are not ideal, but its antifungal effect has a certain increase compared to flavonoids. After that, four bacteria were used to test antibacterial experiments of these compounds; compound 5g (MIC = 0.5, 0.125 mg/L) showed significant inhibitory activity against Staphylococcus aureus and Salmonella gallinarum compared with novobiocin (MIC = 2, 0.25 mg/L). Compound 5s exhibited broad spectrum antibacterial activity (MIC = 1, 0.5, 2, 0.05 mg/L) against four bacteria. The selected compounds 5g and 5s exhibit potent inhibition against Topo II and Topo IV with IC50 values (0.25–16 mg/L). Molecular docking model showed that the compounds 5g and 5s can bind well to the target by interacting with amino acid residues. It will provide some valuable information for the commercial antibacterial agents.

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Acknowledgements

This work was supported by The Basic Science Research Fund Program of ICBR (1632017005), Natural Science Foundation of Education Committee of Anhui Province (KJ2018A0162) and National Key R&D Program of China (Project No. 2017YFD0600805). We are grateful to Prof. Hai-Liang Zhu (State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing) for computational molecular docking assistance.

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Authors and Affiliations

  1. School of Science, Anhui Agricultural University, Hefei, 230036, People’s Republic of China

    Xian-Hai Lv, Hao Liu & Wei Wang

  2. School of Plant Protection, Anhui Agricultural University, Hefei, 230036, People’s Republic of China

    Zi-Li Ren & Hai-Qun Cao

  3. International Center for Bamboo and Rattan, 8 Fu Tong East Street, Beijing, 100714, People’s Republic of China

    Feng Tang

  4. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore

    Xian-Hai Lv

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  1. Xian-Hai Lv
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  2. Hao Liu
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  4. Wei Wang
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  5. Feng Tang
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Correspondence to Feng Tang or Hai-Qun Cao.

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Lv, XH., Liu, H., Ren, ZL. et al. Design, synthesis and biological evaluation of novel flavone Mannich base derivatives as potential antibacterial agents. Mol Divers 23, 299–306 (2019). https://doi.org/10.1007/s11030-018-9873-9

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  • DOI: https://doi.org/10.1007/s11030-018-9873-9

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