The synthesis,structure-toxicity relationship of cisplatin derivatives for the mechanism research of cisplatin-induced nephrotoxicity |
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Authors: | Jing Hu Tian-Ming Wu Hong-Ze Li Ze-Ping Zuo Ying-Lan Zhao Li Yang |
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Institution: | Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China |
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Abstract: | Cisplatin is a widely used antineoplastic drug, while its nephrotoxicity limits the clinical application. Although several mechanisms contributing to nephrotoxicity have been reported, the direct protein targets are unclear. Herein we reported the synthesis of 29 cisplatin derivatives and the structure-toxicity relationship (STR) of these compounds with MTT assay in human renal proximal tubule cells (HK-2) and pig kidney epithelial cells (LLC-PK1). To the best of our knowledge, this study represented the first report regarding the structure-toxicity relationship (STR) of cisplatin derivatives. The potency of biotin-pyridine conjugated derivative 3 met the requirement for target identification, and the preliminary chemical proteomics results suggested that it is a promising tool for further target identification of cisplatin-induced nephrotoxicity. |
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Keywords: | Cisplatin Nephrotoxicity Structure-toxicity relationship (STR) Biotin labeling Chemical proteomics Target identification |
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