Investigation of potential descriptors of chemical compounds on prevention of nephrotoxicity via QSAR approach

Hung-Jin Huang; Yu-Hsuan Lee; Chu-Lin Chou; Cai-Mei Zheng; Hui-Wen Chiu

doi:10.1016/j.csbj.2022.04.013

Investigation of potential descriptors of chemical compounds on prevention of nephrotoxicity via QSAR approach

Comput Struct Biotechnol J. 2022 Apr 15:20:1876-1884. doi: 10.1016/j.csbj.2022.04.013. eCollection 2022.

Authors

Hung-Jin Huang¹, Yu-Hsuan Lee², Chu-Lin Chou^{1

3

4

5}, Cai-Mei Zheng^{1

3

4}, Hui-Wen Chiu^{4

6

7}

Affiliations

¹ Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Department of Cosmeceutics, China Medical University, Taichung, Taiwan.
³ Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
⁴ TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.
⁵ Division of Nephrology, Department of Internal Medicine, Hsin Kuo Min Hospital, Taipei Medical University, Taoyuan City, Taiwan.
⁶ Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.

Abstract

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.

Keywords: AKI, acute kidney injury; CKD, chronic kidney disease; DIKD, drug-induced kidney disease; ESRD, end‐stage renal disease; GFA, genetic function approximation; GFR, glomerular filtration rate; Genetic algorithm; KCSF, keratinocyte serum-free; Nephrotoxicity; PBS, phosphate buffered saline; QSAR; QSAR, quantitative structure-activity relationship; SRB, sulforhodamine B.