2-Azido-4-nitrophenol is a light-sensitive antibacterial protonophore

IF 4.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioelectrochemistry Pub Date : 2025-07-21 DOI:10.1016/j.bioelechem.2025.109055

Alexander M. Firsov , Ljudmila S. Khailova , Pavel A. Nazarov , Maxim Ukraintsev , Roman S. Kirsanov , Sergei I. Kovalchuk , Konstantin G. Lyamzaev , Alisa A. Panteleeva , Galina A. Korshunova , Elena A. Kotova , Yuri N. Antonenko

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引用次数: 0

Abstract

The azide-containing analogue 2-azido-4-nitrophenol (NPA) of the classical mitochondrial uncoupler 2,4-dinitrophenol (DNP) was actively used in 1970s as a tool for searching the binding sites of OxPhos uncouplers on mitochondrial proteins. Here, we report data on the protonophoric, uncoupling and cytotoxic activity of this compound. Artificial bilayer lipid membrane (BLM) experiments revealed much higher potency of NPA compared to DNP in the induction of proton-selective transmembrane electric current. Accordingly, NPA was more effective than DNP in both decreasing membrane potential and stimulating respiration of isolated rat liver mitochondria. NPA also exhibited higher depolarizing and cytotoxic activity towards mammalian cell culture, and was more potent than DNP in suppressing growth of both gram-negative (Escherichia coli) and gram-positive (Bacillus subtilis) bacteria. In all these systems, the activity of NPA but not that of DNP was abolished upon UV illumination. As shown by capillary electrophoresis and LC-MS analysis, UV light induced degradation of NPA to products lacking protonophoric activity, unlike DNP, which appeared to be light-insensitive. Therefore, NPA can be considered as a light-sensitive protonophore that is able to inhibit bacterial growth and promote mitophagy in mammalian cells.

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2-叠氮-4-硝基苯酚是一种光敏抗菌质子载体

经典线粒体解偶联剂2,4-二硝基苯酚（DNP）的含叠氮化物类似物2-叠氮化物-4-硝基苯酚（NPA）在20世纪70年代被积极用于寻找OxPhos解偶联剂在线粒体蛋白上的结合位点。在这里，我们报告了该化合物的质子亲和性、解偶联性和细胞毒性活性的数据。人工双层脂膜（BLM）实验表明，NPA在诱导质子选择性跨膜电流方面比DNP具有更高的效能。因此，NPA在降低离体大鼠肝脏线粒体膜电位和刺激呼吸方面比DNP更有效。NPA对哺乳动物细胞培养也表现出更高的去极化和细胞毒活性，并且在抑制革兰氏阴性（大肠杆菌）和革兰氏阳性（枯草芽孢杆菌）细菌生长方面比DNP更有效。在所有这些体系中，NPA的活性在紫外线照射下被破坏，而DNP的活性没有被破坏。毛细管电泳和LC-MS分析表明，紫外光诱导NPA降解为缺乏亲原活性的产物，而DNP则表现为光不敏感。因此，NPA可以被认为是一种在哺乳动物细胞中能够抑制细菌生长和促进有丝分裂的光敏原体。

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

Bioelectrochemistry 生物-电化学

CiteScore

9.10

自引率

6.00%

发文量

238

审稿时长

38 days

期刊介绍： An International Journal Devoted to Electrochemical Aspects of Biology and Biological Aspects of Electrochemistry Bioelectrochemistry is an international journal devoted to electrochemical principles in biology and biological aspects of electrochemistry. It publishes experimental and theoretical papers dealing with the electrochemical aspects of: • Electrified interfaces (electric double layers, adsorption, electron transfer, protein electrochemistry, basic principles of biosensors, biosensor interfaces and bio-nanosensor design and construction. • Electric and magnetic field effects (field-dependent processes, field interactions with molecules, intramolecular field effects, sensory systems for electric and magnetic fields, molecular and cellular mechanisms) • Bioenergetics and signal transduction (energy conversion, photosynthetic and visual membranes) • Biomembranes and model membranes (thermodynamics and mechanics, membrane transport, electroporation, fusion and insertion) • Electrochemical applications in medicine and biotechnology (drug delivery and gene transfer to cells and tissues, iontophoresis, skin electroporation, injury and repair). • Organization and use of arrays in-vitro and in-vivo, including as part of feedback control. • Electrochemical interrogation of biofilms as generated by microorganisms and tissue reaction associated with medical implants.