A novel pyrazolone complex P-FAH-Cu-bpy induces death of Escherichia coli and Staphylococcus aureus by disrupting...

A novel pyrazolone-based copper complex [Cu(L)(bpy)]∙CH3OH (P-FAH-Cu-bpy) was synthesized and previously characterized to have antitumor properties. This study aimed to investigate its antibacterial properties and action modes against Escherichia coli and Staphylococcus aureus. By agar diffusion assay, P-FAH-Cu-bpy showed strong antibacterial activity against E. coli and S. aureus with the diameter of inhibition zone of 10.17-12.50 mm and 11.83-14 mm, respectively. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the complex were 1.5 and 3 μM, respectively. Destroyed bacteria cells and debris were clearly observed by SEM. At 2 MIC and 4 MIC of P-FAH-Cu-bpy, 1.1683 and 1.9083 pg copper per cell was taken by E. coli, and 4.5670 and 8.5250 pg per cell by S. aureus, respectively. Multi-step resistance selection showed both bacteria were sensitive to P-FAH-Cu-bpy without induction of resistance within 30 generations. With P-FAH-Cu-bpy treatment, the release of nucleotides and proteins and alkaline phosphatase was increased, but the activity of K⁺-Na⁺-ATPase and Ca²⁺-Mg²⁺-ATPase and membrane conductivity were decreased in both pathogens. In conclusion, P-FAH-Cu-bpy induced death of both bacteria by destroying the cell membrane structure and blocking energy and exhibited strong antibacterial activity against E. coli and S. aureus without inducing microbial resistance.