A Novel Artificial Enzyme for In Vivo Free Radical Elimination

活性氧(ROS^1)被认为与许多疾病的发病机制有关，如动脉粥样硬化、癌症和阿尔茨海默病。它们的毒性作用被病理事件放大，包括中性粒细胞激活、高氧、氧化还原活性药物的代谢、辐射暴露和缺血/再灌注。随后，过量产生的ROS，如超氧阴离子(O_2^&t；-&gt；)，导致膜的脂质过氧化损伤，以及对蛋白质和核酸的攻击。因此，抗氧化酶在ROS介导的损伤和疾病的治疗中是有用的。我们合成了一种用于提高血液循环半衰期的大分子锰卟啉。然而，这些锰卟啉缺乏靶向过量产生O_2的细胞的能力，尽管选择性地将SOD模拟物输送到每个特定的细胞中有望成为各种治疗的激进方法。在本研究中，我们合成了一种新的SOD模拟物来消除体内的自由基。我们合成了新型的金属卟啉类化合物作为超氧化物歧化酶的模拟物。此外，我们还展示了具有超氧化物歧化酶活性的金属卟啉类化合物的抗癌作用。最后，我合成了含有金属卟啉衍生物的新型药物载体作为超氧化物歧化酶的模拟物。

Reactive oxygen species (ROS^1) are considered to be implicated in the pathogenesis of a number of diseases, such as atherosclerosis, cancer, and Alzheimer's disease. Their toxic effects are amplified by pathological events including neutrophil activation, hyperoxia, metabolism of redox-active drugs, radiation exposure, and ischemia/reperfusion. Subsequently, the overproduced ROS,'such as superoxide radical anion (O_2^<.->), cause the membrane damage resulting from lipid peroxidation, as well as the attack on proteins and nucleic acids. Therefore, antioxidant enzymes are useful for the therapy of ROS-mediated injuries and diseases. We have synthesized a macromolecular Mn-porphyrin for enhancing half-life in the blood circulation. However, these Mn-porphyrins lack the ability to target the cells overproducing O_2^<.->, although the selective delivery of SOD mimics into every particular cell is promising for a radical approach to various therapyIn this study, we have synthesized a new SOD mimic to eliminate in vivo free radicals. We have synthyesized novel metalloporphyrin derivatives as SOD mimics. In addition, we have demonstrated the anticancer effects of metalloporphyrin derivatives with SOD activity. Finally, I have synthesized novel drug carriers containing metalloporphyrin derivatives as SOD mimics.