School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia.
Bioorg Med Chem Lett. 2009 Dec 15;19(24):7003-6. doi: 10.1016/j.bmcl.2009.09.120. Epub 2009 Oct 7.
Tranilast is an anti-inflammatory drug in use for asthma and atopic dermatitis. In studies over the last decade it has been revealed that tranilast can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. We report a structure-activity study aimed at optimizing the antifibrotic activity of tranilast. A series of cinnamoyl anthranilates were prepared and assessed for their ability to prevent TGF-beta-stimulated production of collagen in cultured renal mesangial cells. We reveal derivatives with improved potency and reduced cellular toxicity relative to tranilast. 3-Methoxy-4-propargyloxycinnamoyl anthranilate reduces albuminuria in a rat model of progressive diabetes, and thus has potential as an innovative treatment for diabetic nephropathy.
曲尼司特是一种用于治疗哮喘和特应性皮炎的抗炎药物。在过去十年的研究中发现，曲尼司特可以减少糖尿病时肾脏发生的纤维化，从而延缓和/或预防肾功能障碍。我们报告了一项旨在优化曲尼司特抗纤维化活性的结构-活性研究。合成了一系列肉桂酰基邻氨基苯甲酸酯，并评估了它们在体外培养的肾小球系膜细胞中抑制 TGF-β刺激胶原产生的能力。我们发现相对于曲尼司特，这些衍生物具有更好的活性和更低的细胞毒性。3-甲氧基-4-丙烯酰氧基肉桂酰基邻氨基苯甲酸酯可减少糖尿病进展大鼠模型中的蛋白尿，因此具有作为治疗糖尿病肾病的创新疗法的潜力。
