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N-substituted piperazinyl sarafloxacin derivatives: synthesis and in vitro antibacterial evaluation

DARU Journal of Pharmaceutical Sciences volume 26, pages 199–207 (2018)Cite this article

Abstract

Background

Fluoroquinolones (FQs) are compounds of major interest with broad antimicrobial activities against community and hospital-acquired infections such as respiratory tract infections (nosocomial pneumonia, chronic bronchitis and tuberculosis), skin and soft tissue infections, bone and joint infections, intra-abdominal infections and sexually transmitted diseases. This broad range of activities along with favorable pharmacokinetic and low toxicity introduced this class of compounds as important antimicrobial chemotherapy agents. The rapid increase in prevalence of FQs resistant microbes in environment motivated medicinal chemists to discover new quinolone-based compounds with potent activities against Gram-positive bacteria.

Methods

The designed compounds were prepared through the two-component reaction between aromatic α-haloketones or α-halooximes and sarafloxacin in the presence of NaHCO3 in DMF, affording the corresponding N-[2-(aryl-3-yl) ethyl] piperazinyl quinolone derivatives in good yields. All synthesized compounds were evaluated for antibacterial activities against Gram-positive [Staphylococcus aureus ATCC 6538p, Micrococcus luteus, ATCC 1110, Staphylococcus epidermidis ATCC 12228 and Bacillus subtilis ATCC 6633] and Gram-negative [Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 10031 Pseudomonas aeruginosa ATCC 9027 and Serratia marcescens PTCC 1111] bacteria.

Results

The antibacterial activities of 24 new compounds were reported as MIC values in comparison to sarafloxacin. The most active compound, 4 g, exhibited similar inhibitory activity against Gram-positive bacteria including S. aureus, S. epidermidis and B. subtilis compared to positive control. Furthermore, benzyloxime incorporated derivatives (4 s-4x) showed poor activity against all tested strains, except 4x.

Conclusion

The obtained results indicated that the synthesized compounds containing substituted piperazine moiety at the C-7 position displayed same or weak inhibitory activities compared to sarafloxacin.

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Acknowledgments

The authors declare no conflict of interests. This work was supported by a grant from the Iranian National Science Foundation (INSF); Grant no. 93023097.

Author information

Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

    Ali Asadipour

  2. Environmental Health Engineering Research Center, Kerman University of Medical Sciences, Kerman, Iran

    Ali Asadipour

  3. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Mohammad Hassan Moshafi, Ghazaleh Ilbeigi, Keivan Beiki & Ehsan Soleimani

  4. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

    Leila Khosravani, Setareh Moghimi, Elham Amou, Loghman Firoozpour & Alireza Foroumadi

  5. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Alireza Foroumadi

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  1. Ali Asadipour
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  2. Mohammad Hassan Moshafi
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  3. Leila Khosravani
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  5. Elham Amou
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  6. Loghman Firoozpour
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  7. Ghazaleh Ilbeigi
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  8. Keivan Beiki
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  9. Ehsan Soleimani
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  10. Alireza Foroumadi
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Correspondence to Alireza Foroumadi.

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Asadipour, A., Moshafi, M.H., Khosravani, L. et al. N-substituted piperazinyl sarafloxacin derivatives: synthesis and in vitro antibacterial evaluation. DARU J Pharm Sci 26, 199–207 (2018). https://doi.org/10.1007/s40199-018-0226-0

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  • DOI: https://doi.org/10.1007/s40199-018-0226-0

Keywords

  • Antibacterial activity
  • Quinolones
  • Synthesis
  • Gram-positive bacteria