Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Mini Rev Med Chem. 2019;19(4):281-291. doi: 10.2174/1389557518666181009141231.
Glyoxalase system is a ubiquitous system in human cells which has been examined thoroughly for its role in different disease conditions. It is composed of Glyoxalase-I (Glo-I) and Glyoxalase- II which perform an essential metabolic process inside the cell by detoxifying endogenous harmful metabolites, mainly methylglyoxal (MG) into non-toxic D-lactic acid. Tumor cells are well-known for their high metabolic rate which results in elevated levels of toxic metabolites. The over-expression of Glo-I in tumor cells makes this enzyme a pivotal target for anticancer drug development. Glo-I is metalloenzyme with two polypeptide chains and encompasses two active sites with an integral zinc atoms at their center. This review aims to highlight the important role of Glo-I in different pathogenic conditions, and more importantly, it provides a thorough discussion of all known human Glo-I inhibitors since its discovery, a hundred years ago, up to date. It embraces the different classes they belong to, their design and chemical structures. We believe this review will help guide the design of novel and potent human Glo-I inhibitors by providing a handy reference for interested researchers in this target.
糖氧还蛋白系统是一种普遍存在于人类细胞中的系统，其在不同疾病状态下的作用已经被深入研究。它由 Glyoxalase-I (Glo-I) 和 Glyoxalase- II 组成，通过将内源性有害代谢物（主要是甲基乙二醛 (MG)）转化为无毒的 D-乳酸，在细胞内执行重要的代谢过程。肿瘤细胞以其高代谢率而闻名，这导致有毒代谢物水平升高。肿瘤细胞中 Glo-I 的过度表达使该酶成为抗癌药物开发的关键靶标。Glo-I 是一种金属酶，由两条多肽链组成，包含两个活性位点，中心有一个完整的锌原子。本综述旨在强调 Glo-I 在不同发病机制中的重要作用，更重要的是，它全面讨论了自 100 年前发现以来所有已知的人类 Glo-I 抑制剂，直至今日。它包括它们所属的不同类别、它们的设计和化学结构。我们相信，通过为对此靶点感兴趣的研究人员提供便捷的参考，本综述将有助于指导新型强效人类 Glo-I 抑制剂的设计。
