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<p>Disruption of the mycobacterial redox homeostasis leads to irreversible stress induction and cell death. Hydroquinone scaffolds, as a new type of redox cycling anti-tuberculosis chemotypes, exhibit potent bactericidal activity against non-replicating, nutrient-deprived phenotypically drug-resistant bacteria. Evidences from microbiological, biochemical, and genetic studies indicate that the redox-driven mode of action relies on the reduction of quinones by type II NADH dehydrogenase (NDH2), generating reactive oxygen species (ROS) of bactericidal level. This study demonstrates that (<i>S</i>)-Peniphenone D possesses significant resistance to <i>Mycobacterium marinum</i> (<i>M. marinum</i>) infection, as it enables redox cycling within <i>M. marinum</i> cells, ROS production, and reduction of intracellular NADH levels. The results suggest that hydroquinone compounds, due to their distinctive biological activities, could serve as novel sources for antibacterial drugs, particularly in developing scaffolds for new anti-tuberculosis agents.</p>

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Inhibitors of NADH–O-methylquinone compound a class of antitubercular drugs

  • 期刊论文

  • 发表日期：

    2025年1月25日

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  • Dongzi Lin,
  • Cheng Xu,
  • Changyou Gan,
  • Bihua Ou,
  • Fengxian Luo,
  • Zhigang She,
  • Lei Zhou,
  • Zhenhua Chen

摘要

Disruption of the mycobacterial redox homeostasis leads to irreversible stress induction and cell death. Hydroquinone scaffolds, as a new type of redox cycling anti-tuberculosis chemotypes, exhibit potent bactericidal activity against non-replicating, nutrient-deprived phenotypically drug-resistant bacteria. Evidences from microbiological, biochemical, and genetic studies indicate that the redox-driven mode of action relies on the reduction of quinones by type II NADH dehydrogenase (NDH2), generating reactive oxygen species (ROS) of bactericidal level. This study demonstrates that (S)-Peniphenone D possesses significant resistance to Mycobacterium marinum (M. marinum) infection, as it enables redox cycling within M. marinum cells, ROS production, and reduction of intracellular NADH levels. The results suggest that hydroquinone compounds, due to their distinctive biological activities, could serve as novel sources for antibacterial drugs, particularly in developing scaffolds for new anti-tuberculosis agents.