Lysosomal-targeted anticancer half-sandwich iridium(III) complexes modified with lonidamine amide derivatives |
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Authors: | Yongkang Xie Shumiao Zhang Xingxing Ge Wenli Ma Xiaolin He Yao Zhao Juan Ye Hongmin Zhang Anwei Wang Zhe Liu |
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Institution: | 1. Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165 China;2. CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China |
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Abstract: | Ten half-sandwich iridium complexes containing lonidamine amide derivatives were synthesized and characterized. Unlike lonidamine, which acts on mitochondria, its iridium complexes successfully targeted lysosomes and induced lysosomal damage. Antiproliferation studies showed that most of the complexes have higher anticancer activity against A549 and HeLa cells than cisplatin. The antitumor activity of complex 6 is 2.69 times that of cisplatin against A549 cells. We also performed antitumor tests on ligands L1 and L5, and proved that they exhibit excellent antitumor activity only after binding to the metal center. The bovine serum albumin (BSA) binding test showed that the complexes had the ability to bind to BSA, and they interact with BSA by a static mechanism. The complexes can also cause changes in mitochondrial membrane potential and can produce active oxygen species better than active control. NADH/NAD+ transformation experiments were used to determine if the production of ROS was caused by the transformation of NADH/NAD+. We also explored the way that the complexes enter cells. |
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Keywords: | anticancer bioimaging iridium complexes lonidamine lysosome targeted |
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