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新型吡哆醇衍生物B6NO的制备、抗氧化性能及增加细胞内一氧化氮的能力

Preparation, Antioxidant Properties and Ability to Increase Intracellular NO of a New Pyridoxine Derivative B6NO.

作者信息

Balakina Anastasia, Prikhodchenko Tatyana, Amozova Vera, Stupina Tatyana, Mumyatova Victoria, Neganova Margarita, Yakushev Ilya, Kornev Alexey, Gadomsky Svyatoslav, Fedorov Boris, Mishchenko Denis

机构信息

Institute of Problems of Chemical Physics, RAS, 142432 Chernogolovka, Russia.

Institute of Physiologically Active Compounds, RAS, 142432 Chernogolovka, Russia.

出版信息

Antioxidants (Basel). 2021 Sep 13;10(9):1451. doi: 10.3390/antiox10091451.

Abstract

In the case of various pathologies, an imbalance between ROS generation and the endogenous AOS can be observed, which leads to excessive ROS accumulation, intensification of LPO processes, and oxidative stress. For the prevention of diseases associated with oxidative stress, drugs with antioxidant activity can be used. The cytotoxic, antioxidant, and NO-donor properties of the new hybrid compound B6NO (di(3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridinium) salt of 2-(nitrooxy)butanedioic acid) were studied. It was determined that B6NO chelates iron ions by 94%, which indicates B6NO's ability to block the Fenton reaction. The hybrid compound B6NO inhibits the process of initiated lipid peroxidation more effectively than pyridoxine. It was shown that B6NO exhibits antioxidant properties by decreasing ROS concentration in normal cells during the oxidative stress induction by -Butyl peroxide. At the same time, the B6NO antioxidant activity on tumor cells was significantly lower. B6NO significantly increases the intracellular nitrogen monoxide accumulation and showed low cytotoxicity for normal cells (IC > 4 mM). Thus, the results indicate a high potential of the B6NO as an antioxidant compound.

摘要

在各种病理情况下,可以观察到活性氧生成与内源性抗氧化系统之间的失衡,这会导致活性氧过度积累、脂质过氧化过程加剧以及氧化应激。为了预防与氧化应激相关的疾病,可以使用具有抗氧化活性的药物。研究了新型杂化化合物B6NO(2-(硝基氧基)丁二酸二(3-羟基-4,5-双(羟甲基)-2-甲基吡啶鎓)盐)的细胞毒性、抗氧化和一氧化氮供体特性。结果表明,B6NO对铁离子的螯合率为94%,这表明B6NO具有阻断芬顿反应的能力。杂化化合物B6NO比吡哆醇更有效地抑制引发的脂质过氧化过程。结果表明,在叔丁基过氧化物诱导氧化应激期间,B6NO通过降低正常细胞中的活性氧浓度而表现出抗氧化特性。同时,B6NO对肿瘤细胞的抗氧化活性明显较低。B6NO显著增加细胞内一氧化氮的积累,并且对正常细胞显示出低细胞毒性(IC>4 mM)。因此,结果表明B6NO作为一种抗氧化化合物具有很高的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a896/8465670/fe058a962ed8/antioxidants-10-01451-g001.jpg

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