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

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2025-01-25 DOI:10.1007/s11030-025-11117-6

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

引用次数: 0

Abstract

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.

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NADH-O-甲基醌抑制剂是一类抗结核药物。

分枝杆菌氧化还原稳态的破坏导致不可逆的应激诱导和细胞死亡。对苯二酚支架作为一种新型氧化还原循环抗结核化学型，对非复制、营养剥夺的表型耐药细菌具有较强的杀菌活性。微生物学、生物化学和遗传学研究表明，氧化还原驱动的作用模式依赖于II型NADH脱氢酶（NDH2）对醌的还原，产生具有杀菌水平的活性氧（ROS）。该研究表明，(S)-Peniphenone D对海洋分枝杆菌（m.m arinum）感染具有显著的抗性，因为它能够在m.m arinum细胞内进行氧化还原循环，产生ROS，并降低细胞内NADH水平。结果表明，对苯二酚类化合物由于其独特的生物活性，可以作为抗菌药物的新来源，特别是在开发新的抗结核药物支架方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;