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Design, synthesis, and antibacterial evaluation of new Schiff’s base derivatives bearing nitroimidazole and pyrazole nuclei as potent E. coli FabH inhibitors

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Abstract

New Schiff’s base derivatives 5a–j have been synthesized by reaction between 5-aryloxypyrazole-4-carbaldehydes 3a–j and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetohydrazide 4 in the presence of nickel (II) nitrate as a catalyst in ethanol at room temperature with good yield (75–88 %). All compounds were tested for antibacterial properties and inhibition of E. coli FabH. Of the compounds studied, the majority of the compounds showed effective antibacterial properties and inhibition of E. coli FabH activity. Compound 5i showed the most effective inhibition (IC50 = 4.6 ± 0.2 µM) by binding into the active site of the E. coli FabH receptor with minimum binding energy (ΔG b = −54.2961 kcal/mol). The binding was stabilized by two hydrogen bonds, two π–π, and three π–cation interactions.

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Acknowledgments

The work was financed by National Natural Science Foundation of China (No. J1103512).

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Authors and Affiliations

  1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, People’s Republic of China

    Chetan B. Sangani, Jigar A. Makwana, Yong-Tao Duan & Hai-Liang Zhu

  2. Chemistry Department, Government Science College, Gandhinagar, 382015, Gujarat, India

    Umesh P. Tarpada, Yogesh S. Patel, Ketan B. Patel & Vivek N. Dave

Authors
  1. Chetan B. Sangani
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  2. Jigar A. Makwana
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  3. Yong-Tao Duan
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  5. Yogesh S. Patel
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  6. Ketan B. Patel
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  8. Hai-Liang Zhu
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Correspondence to Chetan B. Sangani or Hai-Liang Zhu.

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Sangani, C.B., Makwana, J.A., Duan, YT. et al. Design, synthesis, and antibacterial evaluation of new Schiff’s base derivatives bearing nitroimidazole and pyrazole nuclei as potent E. coli FabH inhibitors. Res Chem Intermed 41, 10137–10149 (2015). https://doi.org/10.1007/s11164-015-2018-1

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  • DOI: https://doi.org/10.1007/s11164-015-2018-1

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