Effects of histidin-2-ylidene vs. imidazol-2-ylidene ligands on the anticancer and antivascular activity of complexes of ruthenium, iridium, platinum, and gold
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27491634
DOI
10.1016/j.jinorgbio.2016.07.021
PII: S0162-0134(16)30222-7
Knihovny.cz E-zdroje
- Klíčová slova
- Anticancer agent, Gold complex, Histidin-2-ylidene, N-heterocyclic carbene complex, Platinum complex, Vascular-disrupting agent,
- MeSH
- imidazoly * chemická syntéza chemie farmakologie MeSH
- iridium * chemie farmakologie MeSH
- kuřecí embryo MeSH
- lidé MeSH
- melanom farmakoterapie metabolismus patologie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- patologická angiogeneze farmakoterapie metabolismus patologie MeSH
- platina * chemie farmakologie MeSH
- protinádorové látky * chemická syntéza chemie farmakologie MeSH
- ruthenium * chemie farmakologie MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zlato * chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imidazoly * MeSH
- iridium * MeSH
- platina * MeSH
- protinádorové látky * MeSH
- ruthenium * MeSH
- zlato * MeSH
Couples of N-heterocyclic carbene complexes of ruthenium, iridium, platinum, and gold, each differing only in the carbene ligand being either 1,3-dimethylimidazol-2-ylidene (IM) or 1,3-dimethyl-N-boc-O-methylhistidin-2-ylidene (HIS), were assessed for their antiproliferative effect on seven cancer cell lines, their interaction with DNA, their cell cycle interference, and their vascular disrupting properties. In MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays only the platinum complexes were cytotoxic at single-digit micromolar IC50 concentrations with the (HIS)Pt complex being on average twice as active as the (IM)Pt complex. The former was highly efficacious against cisplatin-resistant HT-29 colon carcinoma cells where the latter had no effect. Both Pt complexes were accumulated by cancer cells and bound to double-helical DNA equally well. Only the (HIS)Pt complex modified the electrophoretic mobility of circular DNA in vitro due to the HIS ligand causing greater morphological changes to the DNA. Both platinum complexes induced accumulation of 518A2 melanoma cells in G2/M and S phase of the cell cycle. A disruption of blood vessels in the chorioallantoic membrane of fertilized chicken eggs was observed for both platinum complexes and the (IM)gold complex. The (HIS)platinum complex was as active as cisplatin in tumor xenografted mice while being tolerated better. We found that the HIS ligand may augment the cytotoxicity of certain antitumoral metal fragments in two ways: by acting as a transmembrane carrier increasing the cellular accumulation of the complex, and by initiating a pronounced distortion and unwinding of DNA. We identified a new (HIS)platinum complex which was highly cytotoxic against cancer cells including cisplatin-resistant ones.
Institute of Biophysics Academy of Sciences of the Czech Republic CZ 61265 Brno Czech Republic
Organic Chemistry Laboratory University of Bayreuth Universitätsstraße 30 95447 Bayreuth Germany
School of Chemistry and Chemical Biology University College Dublin Belfield Dublin 4 Ireland
Citace poskytuje Crossref.org
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