New Quipazine Derivatives Active Against Drug-Resistant Oncogenic Helicobacter pylori Strains with Biofilm

<i>Helicobacter pylori</i> (<i>H. pylori</i>) is regarded as a significant risk factor for gastritis, peptic ulcer disease, and gastric cancer. However, the increasing resistance of <i>H. pylori</i> strains has resulted in low eradication rates and ineffective treatments. Herein, we report on identification of a new quipazine derivative-compound <b>9c</b> (<i>N</i>-(3-chlorobenzyl)-2-(piperazin-1-yl)quinolin-4-amine), which displayed antibacterial properties (MIC range 2-4 µg/mL) against <i>H. pylori</i> CagA-positive reference strains associated with an increased risk of gastric cancer, including metronidazole-resistant ATCC 43504, clarithromycin-resistant ATCC 700684 and susceptible J99 strain, as well as clinical, multidrug-resistant isolate (3CML, resistant to clarithromycin, metronidazole and levofloxacin). Compound <b>9c</b> showed bacteriostatic activity (MBC/MIC ratio > 4), demonstrated antibiofilm-forming properties and prevented auto-aggregation of microbial cells. It also displayed an additive effect in ½ MIC (2 µg/mL) when administered with clarithromycin and/or metronidazole. Compound <b>9c</b> had no impact on gut microbiota reference strains of <i>S. aureus</i>, <i>E. coli</i>, <i>E. faecalis</i> and <i>L. paracasei</i> as well as no hemolytic activity against sheep erythrocytes. Finally, by reducing the viability of the SNU-1 human gastric cancer cell line (IC₅₀ = 3.28 μg/mL), compound <b>9c</b> might offer important implications regarding the oncogenic characteristics of <i>cagA</i>+ <i>H. pylori</i> strains.