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Synthesis, characterization, and biological activity of novel metronidazole-piperazine amides

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Abstract

A new series of metronidazole derivatives containing piperazine rings were prepared via the reaction of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetyl chloride with selected substituted piperazines in the presence of a base. Structures of the new compounds were confirmed by NMR and MS spectral data and by elemental analyses. The antibacterial and anti-parasitic activities of these compounds were evaluated in vitro. Some of the newly synthesized compounds exhibited superior activity against Clostridium sporogenes bacteria compared to the standard drug metronidazole. On the other hand, other derivatives exhibited remarkable antigiardial activity and were found to be more active than metronidazole with IC 50 ranging from 1.8 to 6.7 µg/dm3. 1-Ethyl-4-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]piperazine also exhibited antigiardial activity with similar IC 50 value (7.6 µg/cm3) as compared to the reference drug metronidazole (IC 50 = 7.4 µg/cm3). Similarly, several of the new compounds exhibited significant antitrichomonal activity and found to be more active than metronidazole with IC 50 ranging from 6.7 to 8.65 µg/cm3 as compared to the reference drug metronidazole (8.9 µg/cm3).

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Authors and Affiliations

  1. Department of Chemistry, The University of Jordan, Amman, 11942, Jordan

    Malath A. Al-Qtaitat, Haythem A. Saadeh & Mohammad S. Mubarak

  2. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The University of Jordan, Amman, 11942, Jordan

    Amal G. Al-Bakri

  3. Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Hargobinder Kaur, Kapil Goyal & Rakesh Sehgal

Authors
  1. Malath A. Al-Qtaitat
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  2. Haythem A. Saadeh
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  3. Amal G. Al-Bakri
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  4. Hargobinder Kaur
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  5. Kapil Goyal
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  6. Rakesh Sehgal
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  7. Mohammad S. Mubarak
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Correspondence to Mohammad S. Mubarak.

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Al-Qtaitat, M.A., Saadeh, H.A., Al-Bakri, A.G. et al. Synthesis, characterization, and biological activity of novel metronidazole-piperazine amides. Monatsh Chem 146, 705–712 (2015). https://doi.org/10.1007/s00706-014-1352-0

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  • DOI: https://doi.org/10.1007/s00706-014-1352-0

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