Diab El-Harakeh Mira, Njeim Rachel, Youssef Ali, Youssef Natalie, Eid Assaad A, Bouhadir Kamal H
Department of Chemistry, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Bioorg Med Chem Lett. 2019 Jul 1;29(13):1580-1585. doi: 10.1016/j.bmcl.2019.04.052. Epub 2019 May 2.
Diabetic nephropathy (DN) is one of the most serious complications of diabetes worldwide. It is depicted as the leading cause of end-stage renal disease. Oxidative stress plays a key role in hyperglycemia-induced DN. The preparation and characterization of novel mono-, di-, and trisubstituted-s-triazines endowed with uracil and/or thymine are described in this paper. The synthesis of the title compounds was realized through selective nucleophilic substitution reactions of cyanuric chloride with the corresponding hydrazide nucleobases. In this study, we assessed the effects of these derivatives on the progression of diabetic nephropathy. Our results show that trisubstituted-s-triazines endowed with acylhydrazides attenuate high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. Notably, these derivatives also display anti-oxidative properties. This suggests that the novel trisubstituted-s-triazine derivatives provide renal protection through a reactive oxygen species (ROS)-dependent mechanism. Our data provide evidence that these derivatives may serve as potential therapeutic candidates in the treatment of DN.
糖尿病肾病（DN）是全球糖尿病最严重的并发症之一。它被描述为终末期肾病的主要原因。氧化应激在高血糖诱导的糖尿病肾病中起关键作用。本文描述了具有尿嘧啶和/或胸腺嘧啶的新型单取代、二取代和三取代-s-三嗪的制备与表征。标题化合物的合成是通过三聚氯氰与相应的酰肼核碱基的选择性亲核取代反应实现的。在本研究中，我们评估了这些衍生物对糖尿病肾病进展的影响。我们的结果表明，含有酰肼的三取代-s-三嗪在体外可减轻高糖诱导的肾小球系膜细胞增殖和基质蛋白积累。值得注意的是，这些衍生物还具有抗氧化特性。这表明新型三取代-s-三嗪衍生物通过活性氧（ROS）依赖性机制提供肾脏保护。我们的数据提供了证据，表明这些衍生物可能作为治疗糖尿病肾病的潜在治疗候选物。
