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Article: Anti-Cancer Iron(II) Complexes of Pentadentate N-Donor Ligands: Cytotoxicity, Transcriptomics Analyses, and Mechanisms of Action

TitleAnti-Cancer Iron(II) Complexes of Pentadentate N-Donor Ligands: Cytotoxicity, Transcriptomics Analyses, and Mechanisms of Action
Authors
Issue Date2015
PublisherWiley.
Citation
Chemistry - A European Journal, 2015, v. 21, p. 3062-3072 How to Cite?
AbstractTwo cytotoxic iron(II) complexes [Fe(L)(CH3CN)n](ClO4)2 (L=qpy for Fe-1 a, Py5-OH for Fe-2 a) were synthesized. Both complexes are stable against spontaneous demetalation and oxidation in buffer solutions. Cyclic voltammetry measurements revealed the higher stability of Fe-2 a (+0.82 V vs Fc) against FeII to FeIII oxidation than Fe-1 a (+0.57 V vs Fc). These two complexes display potent cytotoxicity at micromolar level against a panel of cancer cell lines (Fe-1 a=0.8–3.1 μm; Fe-2 a=0.6–3.4 μm), and induce apoptosis that involves caspase activation. Transcriptomic and Connectivity Map analyses revealed that the changes of gene expression induced by Fe-1 a and Fe-2 a are similar to that induced by ciclopirox, an antifungal compound whose mode of action involves formation of intracellular cytotoxic iron chelates. Both Fe-1 a and Fe-2 a caused cellular nuclear DNA damage, as revealed by Comet assay and H2 AX immunofluorescence experiments. The cytotoxicity is associated with production of reactive oxygen species (for Fe-1 a), cell cycle regulation, and stress kinase pathways. The relative contributions of these to the overall cytotoxic mechanism is significantly affected by the structure of penta-N-donor ligand.
Persistent Identifierhttp://hdl.handle.net/10722/215140

 

DC FieldValueLanguage
dc.contributor.authorKwong, WL-
dc.contributor.authorLok, CN-
dc.contributor.authorTSE, CW-
dc.contributor.authorWong, ELM-
dc.contributor.authorChe, CM-
dc.date.accessioned2015-08-21T13:15:38Z-
dc.date.available2015-08-21T13:15:38Z-
dc.date.issued2015-
dc.identifier.citationChemistry - A European Journal, 2015, v. 21, p. 3062-3072-
dc.identifier.urihttp://hdl.handle.net/10722/215140-
dc.description.abstractTwo cytotoxic iron(II) complexes [Fe(L)(CH3CN)n](ClO4)2 (L=qpy for Fe-1 a, Py5-OH for Fe-2 a) were synthesized. Both complexes are stable against spontaneous demetalation and oxidation in buffer solutions. Cyclic voltammetry measurements revealed the higher stability of Fe-2 a (+0.82 V vs Fc) against FeII to FeIII oxidation than Fe-1 a (+0.57 V vs Fc). These two complexes display potent cytotoxicity at micromolar level against a panel of cancer cell lines (Fe-1 a=0.8–3.1 μm; Fe-2 a=0.6–3.4 μm), and induce apoptosis that involves caspase activation. Transcriptomic and Connectivity Map analyses revealed that the changes of gene expression induced by Fe-1 a and Fe-2 a are similar to that induced by ciclopirox, an antifungal compound whose mode of action involves formation of intracellular cytotoxic iron chelates. Both Fe-1 a and Fe-2 a caused cellular nuclear DNA damage, as revealed by Comet assay and H2 AX immunofluorescence experiments. The cytotoxicity is associated with production of reactive oxygen species (for Fe-1 a), cell cycle regulation, and stress kinase pathways. The relative contributions of these to the overall cytotoxic mechanism is significantly affected by the structure of penta-N-donor ligand.-
dc.languageeng-
dc.publisherWiley. -
dc.relation.ispartofChemistry - A European Journal-
dc.rightsPreprint This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article]. Authors are not required to remove preprints posted prior to acceptance of the submitted version. Postprint This is the accepted version of the following article: [full citation], which has been published in final form at [Link to final article]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery. -
dc.titleAnti-Cancer Iron(II) Complexes of Pentadentate N-Donor Ligands: Cytotoxicity, Transcriptomics Analyses, and Mechanisms of Action-
dc.typeArticle-
dc.identifier.emailKwong, WL: kwongwl@hku.hk-
dc.identifier.emailLok, CN: cnlok@hkucc.hku.hk-
dc.identifier.emailWong, ELM: wongella@hkucc.hku.hk-
dc.identifier.emailChe, CM: cmche@hku.hk-
dc.identifier.authorityLok, CN=rp00752-
dc.identifier.authorityWong, ELM=rp00807-
dc.identifier.authorityChe, CM=rp00670-
dc.identifier.doi10.1002/chem.201404749-
dc.identifier.hkuros246905-
dc.identifier.volume21-
dc.identifier.spage3062-
dc.identifier.epage3072-
dc.publisher.placeWeinheim, Germany-

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