Grujicic Jovan, Allen Antiño R
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Antioxidants (Basel). 2024 Nov 23;13(12):1444. doi: 10.3390/antiox13121444.
Reactive oxygen species (ROS) are double-edged swords in biological systems-they are essential for normal cellular functions but can cause damage when accumulated due to oxidative stress. Manganese superoxide dismutase (MnSOD), located in the mitochondrial matrix, is a key enzyme that neutralizes superoxide radicals (O), maintaining cellular redox balance and integrity. This review examines the development and therapeutic potential of MnSOD mimetics-synthetic compounds designed to replicate MnSOD's antioxidant activity. We focus on five main types: Mn porphyrins, Mn salens, MitoQ10, nitroxides, and mangafodipir. These mimetics have shown promise in treating a range of oxidative stress-related conditions, including cardiovascular diseases, neurodegenerative disorders, cancer, and metabolic syndromes. By emulating natural antioxidant defenses, MnSOD mimetics offer innovative strategies to combat diseases linked to mitochondrial dysfunction and ROS accumulation. Future research should aim to optimize these compounds for better stability, bioavailability, and safety, paving the way for their translation into effective clinical therapies.
活性氧(ROS)在生物系统中是双刃剑——它们对于正常细胞功能至关重要,但在因氧化应激而积累时会造成损害。位于线粒体基质中的锰超氧化物歧化酶(MnSOD)是一种关键酶,可中和超氧阴离子自由基(O),维持细胞氧化还原平衡和完整性。本综述探讨了MnSOD模拟物(旨在复制MnSOD抗氧化活性的合成化合物)的发展及治疗潜力。我们重点关注五种主要类型:锰卟啉、锰席夫碱、线粒体辅酶Q10、氮氧化物和锰福地吡。这些模拟物在治疗一系列与氧化应激相关的病症方面已显示出前景,包括心血管疾病、神经退行性疾病、癌症和代谢综合征。通过模拟天然抗氧化防御机制,MnSOD模拟物为对抗与线粒体功能障碍和ROS积累相关的疾病提供了创新策略。未来的研究应致力于优化这些化合物,以提高其稳定性、生物利用度和安全性,为将其转化为有效的临床治疗方法铺平道路。