Synthesis, Structure and Antibacterial Activity of Potent DNA Gyrase Inhibitors: N′-Benzoyl-3-(4-Bromophenyl)-1<i>H</i>-Pyrazole-5-Carbohydrazide Derivatives

<div><p>A total of 19 novel (<b>3a–3s</b>) N′-benzoyl-3-(4-bromophenyl)-1<i>H</i>-pyrazole-5-carbohydrazide analogs were designed, synthesized, and evaluated for biological activities as potential DNA gyrase inhibitors. The results showed that compound <b>3k</b> can strongly inhibit <i>Staphylococcus aureus</i> DNA gyrase and <i>Bacillus subtilis</i> DNA gyrase (with IC₅₀ of 0.15 µg/mL and 0.25 µg/mL, respectively). Structure-activity relationships were also discussed base on the biological and docking simulation results.</p></div

2D Ligand interaction diagram of compound 3k with DNA gyrase.

<p>2D Ligand interaction diagram of compound 3k with DNA gyrase.</p

Crystal packing of the compound 3n.

<p>Crystal packing of the compound 3n.</p

Hydrogen Bond Lengths (Å) and Bond Angles (°) of compound 3n.

<p>Hydrogen Bond Lengths (Å) and Bond Angles (°) of compound 3n.</p

Crystal structure of <i>Staphylococcus aureus</i> DNA gyrase co-complexed with inhibitor.

<p>Crystal structure of <i>Staphylococcus aureus</i> DNA gyrase co-complexed with inhibitor.</p

The receptor surface model with compound 3k.

<p>The receptor surface model with compound 3k.</p

3D model of compound 3n.

<p>3D model of compound 3n.</p

General synthesis of compounds 3a–3s.

<p>General synthesis of compounds 3a–3s.</p

Structure of compound 1 and N′-benzoyl-3-(4-bromophenyl)-1<i>H</i>-pyrazole-5-carbohydrazide analogs and common structural characteristic of compound 1.

<p>Structure of compound 1 and N′-benzoyl-3-(4-bromophenyl)-1<i>H</i>-pyrazole-5-carbohydrazide analogs and common structural characteristic of compound 1.</p

Antimicrobial activity of the synthesized compounds.

<p>Antimicrobial activity of the synthesized compounds.</p