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Synthesis, molecular docking and biological evaluation of novel bis-pyrazole derivatives for analgesic, anti-inflammatory and antimicrobial activities

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Abstract

A new series of bis-pyrazoles were synthesized by Michael addition of hydrazine to chalcones. The starting-material-substituted acetophenones required for the synthesis of chalcones were prepared from itaconic anhydride. The newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, mass spectral and analytical data. All the synthesized compounds were evaluated for in vivo analgesic, anti-inflammatory and in vitro antimicrobial activities. Among the tested compounds, 5a, 5b and 5d showed potential anti-inflammatory and analgesic activities. Further anti-inflammatory results were supported by in silico docking study, in which tested bis-pyrazoles were found to be more selective toward COX-2 (PDB ID: 1CX2) rather than COX-1 (PDB ID: 1CQE). The LD50 values for these products 5(a–l) showed a high safety margin with a dose level >2000 mg/kg. Among all synthesized compounds, N-[4-(5-(4-bromophenyl)-1-phenyl-1H-pyrazol-3-yl)phenyl-2-(3-hydroxy-1-phenyl-1H-pyrazol-4-yl)] acetamide (5b) emerged as most potent molecule with anti-inflammatory, analgesic and antimicrobial properties.

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Acknowledgments

B.N. thanks the UGC for financial assistance through BSR one-time grant for the purchase of chemicals. P.S.N. thanks Manipal Institute of Technology for NMR data and DST-PURSE for financial assistance.

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Authors and Affiliations

  1. Department of Chemistry, Mangalore University, Mangalagangothri, Mangalore, Karnataka, 574 199, India

    Prakash S. Nayak & B. Narayana

  2. Department of Studies in Industrial Chemistry, Mangalore University, Mangalagangothri, Mangalore, Karnataka, 574 199, India

    B. K. Sarojini

  3. Department of Pharmachemistry, N G S M institute of Pharma Sciences, Deralakatte, Mangalore, Karnataka, 575 018, India

    Jennifer Fernades

  4. Department of Biotechnology, NMAM Institute of Technology, Nitte, Karkala, Karnataka, 574 110, India

    B. R. Bharath

  5. Post Graduation Department of Biochemistry, St. Aloysius College, Mangalore, Karnataka, 575 003, India

    L. N. Madhu

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  1. Prakash S. Nayak
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  2. B. Narayana
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  3. B. K. Sarojini
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  4. Jennifer Fernades
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  5. B. R. Bharath
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  6. L. N. Madhu
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Correspondence to B. Narayana.

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Nayak, P.S., Narayana, B., Sarojini, B.K. et al. Synthesis, molecular docking and biological evaluation of novel bis-pyrazole derivatives for analgesic, anti-inflammatory and antimicrobial activities. Med Chem Res 24, 4191–4206 (2015). https://doi.org/10.1007/s00044-015-1467-9

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  • DOI: https://doi.org/10.1007/s00044-015-1467-9

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