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

TL;DR

A new quipazine derivative, compound 9c, shows antibacterial and anti-biofilm activity against drug-resistant Helicobacter pylori strains and may reduce gastric cancer risk.

Contribution

Compound 9c is a novel quipazine derivative effective against multidrug-resistant H. pylori and exhibits anti-cancer potential.

Findings

Compound 9c has antibacterial activity against drug-resistant H. pylori strains with MIC values of 2–4 µg/mL.

It prevents biofilm formation and microbial cell auto-aggregation.

Compound 9c reduces the viability of human gastric cancer cells with an IC50 of 3.28 µg/mL.

Abstract

Helicobacter pylori (H. pylori) is regarded as a significant risk factor for gastritis, peptic ulcer disease, and gastric cancer. However, the increasing resistance of H. pylori strains has resulted in low eradication rates and ineffective treatments. Herein, we report on identification of a new quipazine derivative—compound 9c (N-(3-chlorobenzyl)-2-(piperazin-1-yl)quinolin-4-amine), which displayed antibacterial properties (MIC range 2–4 µg/mL) against H. pylori 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 9c 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 9c had no impact on gut microbiota reference strains of S. aureus, E. coli, E. faecalis and L. paracasei 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 9c might offer important implications regarding the oncogenic characteristics of cagA+ H. pylori strains.

Figures