Huang Hung-Jin, Lee Yu-Hsuan, Chou Chu-Lin, Zheng Cai-Mei, Chiu Hui-Wen
Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Cosmeceutics, China Medical University, Taichung, Taiwan.
Comput Struct Biotechnol J. 2022 Apr 15;20:1876-1884. doi: 10.1016/j.csbj.2022.04.013. eCollection 2022.
Drug-induced nephrotoxicity remains a common problem after exposure to medications and diagnostic agents, which may be heightened in the kidney microenvironment and deteriorate kidney function. In this study, the toxic effects of fourteen marked drugs with the individual chemical structure were evaluated in kidney cells. The quantitative structure-activity relationship (QSAR) approach was employed to investigate the potential structural descriptors of each drug-related to their toxic effects. The most reasonable equation of the QSAR model displayed that the estimated regression coefficients such as the number of ring assemblies, three-membered rings, and six-membered rings were strongly related to toxic effects on renal cells. Meanwhile, the chemical properties of the tested compounds including carbon atoms, bridge bonds, H-bond donors, negative atoms, and rotatable bonds were favored properties and promote the toxic effects on renal cells. Particularly, more numbers of rotatable bonds were positively correlated with strong toxic effects that displayed on the most toxic compound. The useful information discovered from our regression QSAR models may help to identify potential hazardous moiety to avoid nephrotoxicity in renal preventive medicine.
药物诱发的肾毒性在接触药物和诊断试剂后仍然是一个常见问题，在肾脏微环境中这种情况可能会加剧，并导致肾功能恶化。在本研究中，我们评估了14种具有独特化学结构的标记药物对肾细胞的毒性作用。采用定量构效关系（QSAR）方法研究了每种药物与其毒性作用相关的潜在结构描述符。QSAR模型最合理的方程显示，估计的回归系数，如环组件数量、三元环和六元环数量，与对肾细胞的毒性作用密切相关。同时，受试化合物的化学性质，包括碳原子、桥键、氢键供体、负原子和可旋转键，都是有利性质，并促进对肾细胞的毒性作用。特别是，更多数量的可旋转键与最强毒性化合物所表现出的强毒性作用呈正相关。从我们的回归QSAR模型中发现的有用信息可能有助于识别潜在的有害部分，以避免在肾脏预防医学中出现肾毒性。
