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探寻长生不老药:锰卟啉配合物的体内抗氧化作用

Pursuing the Elixir of Life: In Vivo Antioxidative Effects of Manganosalen Complexes.

作者信息

Rouco Lara, González-Noya Ana M, Pedrido Rosa, Maneiro Marcelino

机构信息

Departamento de Química Inorgánica, Facultade de Ciencias, Universidade de Santiago de Compostela, 27002 Lugo, Spain.

Departamento de Química Inorgánica, Facultade de Química, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

出版信息

Antioxidants (Basel). 2020 Aug 10;9(8):727. doi: 10.3390/antiox9080727.

Abstract

Manganosalen complexes are coordination compounds that possess a chelating salen-type ligand, a class of bis-Schiff bases obtained by condensation of salicylaldehyde and a diamine. They may act as catalytic antioxidants mimicking both the structure and the reactivity of the native antioxidant enzymes active site. Thus, manganosalen complexes have been shown to exhibit superoxide dismutase, catalase, and glutathione peroxidase activities, and they could potentially facilitate the scavenging of excess reactive oxygen species (ROS), thereby restoring the redox balance in damaged cells and organs. Initial catalytic studies compared the potency of these compounds as antioxidants in terms of rate constants of the chemical reactivity against ROS, giving catalytic values approaching and even exceeding that of the native antioxidative enzymes. Although most of these catalytic studies lack of biological relevance, subsequent in vitro studies have confirmed the efficiency of many manganosalen complexes in oxidative stress models. These synthetic catalytic scavengers, cheaper than natural antioxidants, have accordingly attracted intensive attention for the therapy of ROS-mediated injuries. The aim of this review is to focus on in vivo studies performed on manganosalen complexes and their activity on the treatment of several pathological disorders associated with oxidative damage. These disorders, ranging from the prevention of fetal malformations to the extension of lifespan, include neurodegenerative, inflammatory, and cardiovascular diseases; tissue injury; and other damages related to the liver, kidney, or lungs.

摘要

锰-萨伦配合物是一类配位化合物,其具有螯合的萨伦型配体,这是一类通过水杨醛与二胺缩合得到的双席夫碱。它们可以作为催化抗氧化剂,模拟天然抗氧化酶活性位点的结构和反应性。因此,锰-萨伦配合物已被证明具有超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性,并且它们有可能促进清除过量的活性氧(ROS),从而恢复受损细胞和器官中的氧化还原平衡。最初的催化研究根据这些化合物与ROS化学反应的速率常数比较了它们作为抗氧化剂的效力,得出的催化值接近甚至超过天然抗氧化酶。尽管大多数这些催化研究缺乏生物学相关性,但随后的体外研究证实了许多锰-萨伦配合物在氧化应激模型中的有效性。这些合成催化清除剂比天然抗氧化剂便宜,因此在ROS介导的损伤治疗中引起了广泛关注。本综述的目的是关注对锰-萨伦配合物进行的体内研究及其对几种与氧化损伤相关的病理疾病的治疗活性。这些疾病范围从预防胎儿畸形到延长寿命,包括神经退行性疾病、炎症性疾病和心血管疾病;组织损伤;以及与肝脏、肾脏或肺部相关的其他损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e7/7465912/ee254f50fa3f/antioxidants-09-00727-g001.jpg

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