Potential anticancer agent for selective damage to mitochondria or lysosomes: Naphthalimide-modified fluorescent biomarker half-sandwich iridium (III) and ruthenium (II) complexes.

Eur J Med Chem

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. Electronic address:

Published: November 2019

In this work, five naphthalimide-modified half-sandwich iridium and ruthenium complexes ([(η-Cp)Ir(NˆN)Cl]PF, [(η-p-cym)Ru(NˆN)Cl]PF) have been presented. The anticancer activities of the complexes against various cancer cell lines were investigated, among them, complexes 2 and 4 showed better anticancer activity than cisplatin, and their anticancer activity is better than complex 5 without fluorophore. In addition, a series of biological tests of complex 2 were performed using flow cytometry, the results indicated that the complex could induce cell death in a variety of ways. By changing of the ligands, the complexes exhibited different photophysical properties, and the mechanism of action of the complexes entering the cell and inducing apoptosis are different. Moreover, complex 2 successfully targeted mitochondria, while complex 4 targeted lysosomes, causing mitochondrial damage and lysosomal damage to induce apoptosis. Excitingly, complex 2 has good antimetastatic ability to cancer cells. Furthermore, complexes 2 and 4 did not have a significant effect on the NADH binding reaction, but they had a moderate binding ability to BSA.

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http://dx.doi.org/10.1016/j.ejmech.2019.111599DOI Listing

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