Bacci Andrea, Corsi Francesca, Runfola Massimiliano, Sestito Simona, Piano Ilaria, Manera Clementina, Saccomanni Giuseppe, Gargini Claudia, Rapposelli Simona
Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
Pharmaceuticals (Basel). 2022 May 31;15(6):688. doi: 10.3390/ph15060688.
Overproduction of reactive oxygen species (ROS) and alterations in metallostasis are common and related hallmarks in several neurodegenerative diseases (NDDs). Nature-based derivatives always represent an attractive tool in MTDL drug design, especially against ROS in NDDs. On this notion, we designed a new series of 8-quinoline-N-substituted derivatives with a natural antioxidant portion (i.e., lipoic, caffeic, and ferulic acids). These compounds were shown to chelate copper, a metal involved in ROS-induced degeneration, and scavenger oxygen radicals in DPPH assay. Then, selected compounds and were evaluated in an in vitro model of oxidative stress and shown to possess cytoprotective effects in 661W photoreceptor-like cells. The obtained results may represent a starting point for the application of the proposed class of compounds in retinal neurodegenerative diseases such as retinitis pigmentosa (RP), comprising a group of hereditary rod-cone dystrophies that represent a major cause of blindness in patients of working age, where the progression of the disease is a multifactorial event, with oxidative stress contributing predominantly.
活性氧（ROS）的过度产生和金属稳态的改变是几种神经退行性疾病（NDDs）中常见的相关特征。基于天然产物的衍生物在多靶点药物设计中一直是一种有吸引力的工具，尤其是针对神经退行性疾病中的ROS。基于这一概念，我们设计了一系列新的8-喹啉-N-取代衍生物，它们带有天然抗氧化部分（即硫辛酸、咖啡酸和阿魏酸）。这些化合物在DPPH试验中显示出能螯合铜（一种参与ROS诱导变性的金属）并清除氧自由基。然后，对选定的化合物 和 在氧化应激体外模型中进行评估，结果表明它们在661W光感受器样细胞中具有细胞保护作用。所得结果可能代表了将所提出的这类化合物应用于视网膜神经退行性疾病（如色素性视网膜炎（RP））的起点，色素性视网膜炎是一组遗传性视杆-视锥营养不良症，是工作年龄患者失明的主要原因，该病的进展是一个多因素事件，氧化应激起主要作用。
