Rahman Md Mominur, Islam Md Rezaul, Alam Tumpa Mst Afroza, Shohag Sheikh, Ferdous Jannatul, Kajol Saima Akter, Aljohani Abdullah S M, Al Abdulmonem Waleed, Rauf Abdur, Thiruvengadam Muthu
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh.
Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University Buraydah, 52571, Saudi Arabia.
Chem Biol Interact. 2023 Mar 1;373:110375. doi: 10.1016/j.cbi.2023.110375. Epub 2023 Feb 3.
Medicinal chemistry is an interdisciplinary field that incorporates organic chemistry, biochemistry, physical chemistry, pharmacology, informatics, molecular biology, structural biology, cell biology, and other disciplines. Additionally, it considers molecular factors such as the mode of action of the drugs, their chemical structure-activity relationship (SAR), and pharmacokinetic aspects like absorption, distribution, metabolism, elimination, and toxicity. Neurodegenerative disorders (NDs), which are defined by the breakdown of neurons over time, are affecting an increasing number of people. Oxidative stress, particularly the increased production of Reactive Oxygen Species (ROS), plays a crucial role in the growth of various disorders, as indicated by the identification of protein, lipid, and Deoxyribonucleic acid (DNA) oxidation products in vivo. Because of their inherent nature, most biological molecules are vulnerable to ROS, even if they play a role in metabolic parameters and cell signaling. Due to their high polyunsaturated fatty acid content, low antioxidant barrier, and high oxygen uptake, neurons are particularly vulnerable to oxidation by nature. As a result, excessive ROS generation in neurons looks especially harmful, and the mechanisms associated with biomolecule oxidative destruction are several and complex. This review focuses on the formation and management of ROS, as well as their chemical characteristics (both thermodynamic and kinetic), interactions, and implications in NDs.
药物化学是一个跨学科领域,融合了有机化学、生物化学、物理化学、药理学、信息学、分子生物学、结构生物学、细胞生物学及其他学科。此外,它还考虑分子因素,如药物的作用方式、化学结构-活性关系(SAR)以及药代动力学方面,如吸收、分布、代谢、消除和毒性。神经退行性疾病(NDs)是随着时间推移神经元发生退化而定义的疾病,影响着越来越多的人。氧化应激,特别是活性氧(ROS)生成增加,在各种疾病的发展中起着关键作用,体内蛋白质、脂质和脱氧核糖核酸(DNA)氧化产物的鉴定表明了这一点。由于其固有性质,大多数生物分子易受ROS影响,即使它们在代谢参数和细胞信号传导中起作用。由于神经元富含多不饱和脂肪酸、抗氧化屏障低且氧摄取高,其本质上特别容易受到氧化。因此,神经元中过量的ROS生成看起来尤其有害,与生物分子氧化破坏相关的机制多种多样且复杂。本综述重点关注ROS的形成与调控,以及它们的化学特性(热力学和动力学)、相互作用及其在神经退行性疾病中的影响。