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<p><i>Helicobacter pylori (H. pylori)</i> is a widespread pathogen and a significant causative agent of chronic gastritis and peptic ulcers. However, eradication rates are declining rapidly because of increasing antibiotic resistance, and recurrence rates are rising. Quinolone-based regimens were once considered effective treatment options; however, their clinical utility has been substantially limited in recent years by a marked increase in resistance rates worldwide. Therefore, the development of more effective drugs and treatment strategies is crucial for combating <i>H. pylori</i> infections. This study evaluated the in vitro antibacterial activity and cytotoxicity of a series of novel quinolone compounds (provided by the team of Professor Ying-Qian Liu from the School of Pharmacy, Lanzhou University), ultimately identifying two lead compounds, ET-8 and ET-30, for further investigation, with minimum inhibitory concentrations (MICs) of 5.29 micromolar (µM) and 5.20 µM, respectively. Furthermore, ET-8 and ET-30 were also effective against both sensitive and resistant strains of <i>H. pylori.</i> Investigations involving urease inhibition assays, transmission electron microscopy, and adhesion assays suggested that ET-8 and ET-30 likely exert their antibacterial effects by disrupting bacterial morphology, inhibiting adhesion and colonization, and suppressing urease activity. Additionally, RT‒qPCR analysis revealed that these phenotypic changes were accompanied by the downregulation of key virulence and adhesion genes (<i>vacA</i>, <i>cagA</i>, <i>sabA</i>, and <i>babA</i>); however, this correlation does not establish causation, providing a compelling mechanistic hypothesis for the observed antibacterial effects. Collectively, these findings demonstrate that compared with the current fluoroquinolone therapeutic, levofloxacin (LEV), ET-8 and ET-30 exhibit superior antibacterial activity and a more favorable safety profile, highlighting their strong potential as candidate agents for future anti-<i>H. pylori</i> therapies.</p>

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In vitro anti-Helicobacter pylori activity and phenotypic screening of novel quinolone compounds

  • 期刊论文

  • 发表日期：

    2025年11月20日

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  • Yuan-Yuan Wang,
  • Guo-Liang Mou,
  • Xing-Lan Chen,
  • Jin-Xia Yang,
  • Qian Luo,
  • Ye-Ze Dong,
  • Bao-Yuan Xie,
  • De-Kui Zhang,
  • Ying-Qian Liu

摘要

Helicobacter pylori (H. pylori) is a widespread pathogen and a significant causative agent of chronic gastritis and peptic ulcers. However, eradication rates are declining rapidly because of increasing antibiotic resistance, and recurrence rates are rising. Quinolone-based regimens were once considered effective treatment options; however, their clinical utility has been substantially limited in recent years by a marked increase in resistance rates worldwide. Therefore, the development of more effective drugs and treatment strategies is crucial for combating H. pylori infections. This study evaluated the in vitro antibacterial activity and cytotoxicity of a series of novel quinolone compounds (provided by the team of Professor Ying-Qian Liu from the School of Pharmacy, Lanzhou University), ultimately identifying two lead compounds, ET-8 and ET-30, for further investigation, with minimum inhibitory concentrations (MICs) of 5.29 micromolar (µM) and 5.20 µM, respectively. Furthermore, ET-8 and ET-30 were also effective against both sensitive and resistant strains of H. pylori. Investigations involving urease inhibition assays, transmission electron microscopy, and adhesion assays suggested that ET-8 and ET-30 likely exert their antibacterial effects by disrupting bacterial morphology, inhibiting adhesion and colonization, and suppressing urease activity. Additionally, RT‒qPCR analysis revealed that these phenotypic changes were accompanied by the downregulation of key virulence and adhesion genes (vacA, cagA, sabA, and babA); however, this correlation does not establish causation, providing a compelling mechanistic hypothesis for the observed antibacterial effects. Collectively, these findings demonstrate that compared with the current fluoroquinolone therapeutic, levofloxacin (LEV), ET-8 and ET-30 exhibit superior antibacterial activity and a more favorable safety profile, highlighting their strong potential as candidate agents for future anti-H. pylori therapies.