Add time:08/20/2019         Source:sciencedirect.com

Although many N-heterocyclic thiosemicarbazone copper complexes have been proposed as potential anticancer agents, little is known about their intracellular localization in cells. In the present study, we synthesized two fluorescent N-heterocyclic thiosemicarbazone copper complexes, ([CuII(L)(Br)] 1 and [CuII2CuI(L)2(Br)3] 2, where HL is (E)-N,N-dimethyl-2-(quinolin-8-ylmethylene)hydrazinecarbothioamide), to assess their intracellular distribution. Our fluorescence studies demonstrated that complex 1 showed an intense emission band at ca. 510 nm (λex = 405 nm) similar to that of complex 2, albeit with about four times lower emission intensity. Both copper complexes showed significantly greater cytotoxicity toward several tumor cell-types with better IC50 (0.27–0.91 μM) than the HL ligand and cisplatin. Scratching wound healing assay and invasion assay were performed, revealing that the copper complexes have good antimetastatic activity. Confocal fluorescence imaging allowed ascertaining that complex 2 was primarily localized to mitochondria. Further studies revealed that the anticancer mechanisms of complex 2 might involve the mitochondrial-mediated apoptotic pathway, probably caused by the reducing mitochondrial membrane potential and induction of ROS (reactive oxygen species) production. Furthermore, complex 2 exhibited promising cytostatic effects in a three-dimensional HeLa spheroid model.

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