Discovery of novel multi-substituted benzo-indole pyrazole schiff base derivatives with antibacterial activity targeting DNA gyrase.

• 48 benzo-indole pyrazole Schiff base derivatives were designed and synthesized. • Compound 8I-w can act as the most potent DNA gyrase inhibitor in this work. • Modifications on the benzene and pyrazole rings are the keys to potent activity. The design and synthesis of novel multi-substituted benzo-indole pyrazole Schiff base derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activities against Staphylococcus aureus , Listeria monocytogenes , Escherichia coli , and Salmonella. In addition, we selected 20 compounds for the in vitro antibacterial activities assay of 6 drug-resistant bacteria strains. The result revealed compound 8I-w exhibited excellent antibacterial activity against 4 drug-resistant E. coli bacteria strains with IC 50 values of 7.0, 17.0, 13.5, and 1.0 μM, respectively. In vitro enzyme inhibitory assay showed that compound 8I-w displayed potent inhibition against DNA gyrase with IC 50 values of 0.10 μM. The molecular docking model indicated that compounds 8I-w can bind well to the DNA gyrase by interacting with various amino acid residues. This study demonstrated that the compound 8I-w can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides. [ABSTRACT FROM AUTHOR]