Deng, J.Yu, P.Zhang, Z.Wang, J.Cai, J.Wu, NaSun, H.Liang, H.Yang, F.2020-05-262020-06-192020-05-262020-06-192018-10Deng J, Yu P, Zhang Z et al (2018) Designing anticancer copper(II) complexes by optimizing 2-pyridine-thiosemicarbazone ligands. European Journal of Medicinal Chemistry. 158: 442-452.RMSID:212573850http://hdl.handle.net/10454/17847YesTo develop potential next-generation metal anticancer agents, we designed and synthesised five Cu(II) 2-pyridine-thiosemicarbazone complexes by modifying the hydrogen atom at the N-4 position of ligands, and then investigated their structure-activity relationships and anticancer mechanisms. Modification of the N-4 position with different groups caused significant differences in cellular uptake and produced superior antitumor activity. Cu complexes arrested the cell cycle at S phase, leading to down-regulation of levels of cyclin and cyclin-dependent kinases and up-regulation of expression of cyclin-dependent kinase inhibitors. Cu complexes exerted chemotherapeutic effects via activating p53 and inducing production of reactive oxygen species to regulate expression of the B-cell lymphoma-2 family of proteins, causing a change in the mitochondrial membrane potential and release of cytochrome c to form a dimer with apoptosis protease activating factor-1, resulting in activation of caspase-9/3 to induce apoptosis. In addition, Cu complexes inhibited telomerase by down-regulating the c-myc regulator gene and expression of the human telomerase reverse transcriptase.en© 2018 Elsevier Masson SAS. All rights reserved. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.Cu(II) complexesThiosemicarbazoneAnticancerp53TelomeraseArticlehttps://doi.org/10.1016/j.ejmech.2018.09.020CC-BY-NC-ND2020-05-26