Rahbar Samuel, Figarola James L
Department of Diabetes, Beckman Research Institute of the City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA.
Arch Biochem Biophys. 2003 Nov 1;419(1):63-79. doi: 10.1016/j.abb.2003.08.009.
A number of natural or synthetic compounds as AGE inhibitors have been proposed, discovered or currently being advanced by others and us. We have identified two new classes of aromatic compounds; aryl- (and heterocyclic) ureido and aryl (and heterocyclic) carboxamido phenoxyisobutyric acids, and benzoic acid derivatives and related compounds, as potential inhibitors of glycation and AGE formation. Some of these novel compounds also showed "AGE-breaking" activities in vitro. Current evidence is that chelation of transition metals and/or trapping or indirect inhibition of formation of reactive carbonyl compounds are involved in the mechanisms of action of these novel AGE inhibitors and breakers. Here, we review the inhibitors of glycation and AGE-breakers published to date and present the results of our in vitro and in vivo investigations on a number of these novel AGE inhibitors. These AGE-inhibitors and AGE-breakers may find therapeutic use in the treatment of diseases that AGE formation and accumulation may be responsible for their pathogenesis such as diabetes, Alzheimer's, rheumatoid arthritis, and atherosclerosis.
已有许多天然或合成化合物被他人及我们提出、发现或目前正在推进作为晚期糖基化终产物（AGE）抑制剂。我们已鉴定出两类新型芳香族化合物；芳基-（及杂环）脲基和芳基（及杂环）羧酰胺基苯氧基异丁酸，以及苯甲酸衍生物和相关化合物，作为潜在的糖基化和AGE形成抑制剂。这些新型化合物中的一些在体外还表现出“AGE分解”活性。目前的证据表明，过渡金属螯合和/或捕获或间接抑制活性羰基化合物的形成参与了这些新型AGE抑制剂和分解剂的作用机制。在此，我们综述了迄今为止已发表的糖基化抑制剂和AGE分解剂，并展示了我们对多种这些新型AGE抑制剂进行的体外和体内研究结果。这些AGE抑制剂和AGE分解剂可能在治疗因AGE形成和积累可能导致其发病机制的疾病中找到治疗用途，如糖尿病、阿尔茨海默病、类风湿性关节炎和动脉粥样硬化。
