Renal fibrosis is a renal disorder whereby production of excess fibrous connective tissue in the glomerulus and proximal convoluted tubules will occur in a reparative or reactive process leading to severe conditions like surgery, replacement, etc. Such a condition needs pharmacotherapy with drugs reducing renal overload (captopril) and inflammation (taurine). In this research project, two chemical conjugates of captopril with taurine and glutamic acid were developed using in silico analysis for an improvement in bioavailability with a reduction in inflammation. The stability of these conjugates in sheep kidney cells and in human plasma along with transport across renal cells was investigated using in vitro protocols. The results of these studies have revealed that conjugates have retained desired interactions for transportability across renal epithelial cells and their bioactivity against ACE and TGF-β. Both conjugates A and B were found to be stable over a period of 14 h in plasma and transported nearly 2 times more than captopril across renal epithelial cells. These conjugates were almost entirely hydrolyzed in renal lysosomes over a period of 14 h (87.39 ± 2.59%). Thus a combination of these two conjugates would be an effective chemotherapy to prevent progression of renal fibrosis to renal failure after in vivo studies of these conjugates.

中文翻译：

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卡托普利偶联物在肾纤维化治疗中的计算机设计，合成，表征和药理学评估†

肾纤维化是一种肾脏疾病，在肾小球和近曲小管中会产生多余的纤维结缔组织，这是通过修复或反应过程产生的，从而导致严重的疾病，例如手术，置换等。这种疾病需要药物治疗，并需要减少肾脏超负荷的药物（卡托普利）和炎症（牛磺酸）。在该研究项目中，使用计算机分析法开发了卡托普利与牛磺酸和谷氨酸的两种化学共轭物，以提高生物利用度并减少炎症。使用体外方法研究了这些结合物在绵羊肾细胞和人血浆中的稳定性以及跨肾细胞的转运。协议。这些研究的结果表明，缀合物保留了跨肾脏上皮细胞运输所需的相互作用以及它们对ACE和TGF-β的生物活性。发现缀合物A和缀合物B在血浆中均可以在14小时内保持稳定，并且在肾脏上皮细胞中的转运量是卡托普利的近2倍。这些缀合物在14小时内几乎完全在肾溶酶体中水解（87.39±2.59％）。因此，在结合物的体内研究之后，这两种结合物的组合将是防止肾纤维化发展为肾衰竭的有效化学疗法。