儿茶酚衍生曼尼希碱:自由基调节特性、细胞毒性以及与生物大分子的相互作用。

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Gvozdev M Y, Turomsha I S, Loginova N V, Varfolomeeva E Y, Kovalev R A, Fedorova N D, Ksendzova G A, Osipovich N P, Sverdlov R L
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引用次数: 0

摘要

自由基在生物系统中无处不在,是导致退行性疾病的病因,并参与极其重要的生化过程,而这些过程是由自由基调节剂介导的。研究人员调查了儿茶酚衍生曼尼希碱中脂肪胺取代基对其抗氧化和促氧化活性的影响。研究发现,曼尼希碱结构中儿茶酚分子的存在使其能够作为铜(II)还原剂、高效的铁(II)螯合剂和强效的 DPPH 自由基清除剂。研究发现,清除 DPPH 自由基的合理机制是先形成醌,然后通过迈克尔加成反应与乙醇相互作用。在中性粒细胞呼吸爆发试验中,有几种化合物在微摩尔水平(0.1-10 µM)上表现出微弱的抗氧化活性,而在毫摩尔水平(0.1 mМ)上则表现出强烈的促氧化作用。此外,在使用的最高浓度下,所有合成化合物对真皮成纤维细胞 DF-2 都有明显的细胞毒性,对 T 淋巴细胞也有免疫抑制作用。研究表明,儿茶酚在低分子硫醇存在下的氧化过程中会形成共价加合物,这有助于深入了解它们的细胞毒性和解毒途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Catechol-derived Mannich bases: radical regulatory properties, cytotoxicity and interaction with biomolecules.

Free radicals are ubiquitous in biological systems, being responsible for pathogenesis of degenerative diseases and participating in vitally important biochemical processes, which are mediated by radical regulatory agents. The effects of the aliphatic amine substituents in the catechol-derived Mannich bases on their antioxidant and pro-oxidant activity were investigated. It has been found that the presence of catechol moiety in the structure of Mannich bases allows them to act as Cu(II) reductants, efficient Fe(II) chelators and potent DPPH radical scavengers. It has been found that the plausible mechanism of the DPPH radical scavenging proceeds via quinone formation, followed by their interaction with ethanol via the Michael addition reaction. In the neutrophil respiratory burst assay, several compounds have demonstrated a weak antioxidant activity at the micromolar level (0.1-10 µM), whereas at the millimolar level (0.1 mМ) a strong pro-oxidant effect has been observed. Additionally, at the highest used concentrations a pronounced cytotoxicity against dermal fibroblasts DF-2 and an immunosuppressive effect against T-lymphocytes have been observed for all the synthesized compounds. It has been demonstrated that the oxidation of catechols in the presence of low-molecular thiols results in the formation of covalent adducts, which provides an insight into their cytotoxicity and detoxification pathways.

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来源期刊
Free Radical Research
Free Radical Research 生物-生化与分子生物学
CiteScore
6.70
自引率
0.00%
发文量
47
审稿时长
3 months
期刊介绍: Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.
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