Desai Kaushik, Wu Lingyun
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Recent Pat Cardiovasc Drug Discov. 2007 Jun;2(2):89-99. doi: 10.2174/157489007780832498.
Advanced glycation endproducts (AGEs) are unavoidable byproducts of various metabolic pathways. They are formed by reactive metabolic intermediates such as methylglyoxal (MG), glyoxal, and 3-deoxyglucosone. These reactive intermediates bind to proteins, DNA, and other molecules and disrupt their structures and functions, which leads to different diseases such as vascular complications of diabetes, atherosclerosis, hypertension, Alzheimer's disease, and aging. In recent years, more compounds that prevent the formation of AGEs or degrade the existing AGEs have been produced and patented. They include: 1) aminoguanidine, 2) drugs used in the treatment of type 2 diabetes such as metformin and pioglitazone (patented), 3) angiotensin receptor blockers and angiotensin converting enzyme inhibitors, 4) pentoxyfylline (patented), 5) metal ion chelators desferoxamine and penicillamine, 6) antioxidants such as vitamin C or E, 7) amino group capping agents such as aspirin, 8) enzymes that cause deglycation of Amadori products, the Amadoriases, 9) compounds that mostly break alpha-dicarbonyl cross-links such as phenacylthiazolium bromide and its stable derivative ALT-711 (Alagebrium), and 10) derivatives of aryl ureido and aryl carboxaminido phenoxy isobutyric acids (patented). While some of these anti-AGE compounds are being used in clinical practice (such as metformin, pioglitazone, pentoxyfylline and aspirin) or tested in clinical trials (such as aminoguanidine and ALT-711), most of them are commonly used as experimental tools to investigate the role of AGEs in different disease conditions.
晚期糖基化终末产物（AGEs）是各种代谢途径不可避免的副产物。它们由活性代谢中间体如甲基乙二醛（MG）、乙二醛和3-脱氧葡萄糖醛酮形成。这些活性中间体与蛋白质、DNA和其他分子结合，破坏它们的结构和功能，从而导致不同的疾病，如糖尿病血管并发症、动脉粥样硬化、高血压、阿尔茨海默病和衰老。近年来，更多能够预防AGEs形成或降解现有AGEs的化合物已被生产并获得专利。它们包括：1）氨基胍；2）用于治疗2型糖尿病的药物，如二甲双胍和吡格列酮（已获专利）；3）血管紧张素受体阻滞剂和血管紧张素转换酶抑制剂；4）己酮可可碱（已获专利）；5）金属离子螯合剂去铁胺和青霉胺；6）抗氧化剂，如维生素C或E；7）氨基封端剂，如阿司匹林；8）使阿马多里产物脱糖基化的酶，即阿马多里酶；9）主要破坏α-二羰基交联键的化合物，如溴化苯甲酰噻唑鎓及其稳定衍生物ALT-711（阿格列净）；10）芳基脲基和芳基羧氨基苯氧基异丁酸的衍生物（已获专利）。虽然其中一些抗AGE化合物正在临床实践中使用（如二甲双胍、吡格列酮、己酮可可碱和阿司匹林）或在临床试验中进行测试（如氨基胍和ALT-711），但它们中的大多数通常用作实验工具来研究AGEs在不同疾病状态中的作用。
