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dc.contributor.authorDeng, J.
dc.contributor.authorYu, P.
dc.contributor.authorZhang, Z.
dc.contributor.authorWang, J.
dc.contributor.authorCai, J.
dc.contributor.authorWu, Na (Anna)
dc.contributor.authorSun, H.
dc.contributor.authorLiang, H.
dc.contributor.authorYang, F.
dc.date.accessioned2020-05-26T13:41:34Z
dc.date.accessioned2020-06-19T14:28:50Z
dc.date.available2020-05-26T13:41:34Z
dc.date.available2020-06-19T14:28:50Z
dc.date.issued2018-10
dc.identifier.citationDeng 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.en_US
dc.identifier.urihttp://hdl.handle.net/10454/17847
dc.descriptionYesen_US
dc.description.abstractTo 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_US
dc.description.sponsorshipNatural ScienceFoundation of China (31460232, 21431001, 21561017, 21462004),the Natural Science Foundation of Guangxi (2017GXNSFEA198002,AD17129007), IRT_16R15, Guangxi“Bagui”scholar program to HBSun, and High-Level Innovation Team and Distinguished Scholarprogram of Guangxi universities to F Yang.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.ejmech.2018.09.020en_US
dc.rights© 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.
dc.subjectCu(II) complexesen_US
dc.subjectThiosemicarbazoneen_US
dc.subjectAnticanceren_US
dc.subjectp53en_US
dc.subjectTelomeraseen_US
dc.titleDesigning anticancer copper(II) complexes by optimizing 2-pyridine-thiosemicarbazone ligandsen_US
dc.status.refereedYesen_US
dc.date.Accepted2018-09-08
dc.date.application2018-09-10
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
dc.date.updated2020-05-26T12:41:35Z
refterms.dateFOA2020-06-26T10:16:24Z


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