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

摘要

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, H-1-NMR, C-13-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.