Effects of histidin-2-ylidene vs. imidazol-2-ylidene ligands on the anticancer and antivascular activity of complexes of ruthenium, iridium, platinum, and gold
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27491634
DOI
10.1016/j.jinorgbio.2016.07.021
PII: S0162-0134(16)30222-7
Knihovny.cz E-resources
- Keywords
- Anticancer agent, Gold complex, Histidin-2-ylidene, N-heterocyclic carbene complex, Platinum complex, Vascular-disrupting agent,
- MeSH
- Imidazoles * chemical synthesis chemistry pharmacology MeSH
- Iridium * chemistry pharmacology MeSH
- Chick Embryo MeSH
- Humans MeSH
- Melanoma drug therapy metabolism pathology MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neovascularization, Pathologic drug therapy metabolism pathology MeSH
- Platinum * chemistry pharmacology MeSH
- Antineoplastic Agents * chemical synthesis chemistry pharmacology MeSH
- Ruthenium * chemistry pharmacology MeSH
- Xenograft Model Antitumor Assays MeSH
- Gold * chemistry pharmacology MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Imidazoles * MeSH
- Iridium * MeSH
- Platinum * MeSH
- Antineoplastic Agents * MeSH
- Ruthenium * MeSH
- Gold * 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
References provided by Crossref.org
In vitro anticancer active cis-Pt(II)-diiodido complexes containing 4-azaindoles
