New (arene)ruthenium(II) complexes of 4‑aryl‑4H‑naphthopyrans with anticancer and anti-vascular activities
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29684697
DOI
10.1016/j.jinorgbio.2018.03.013
PII: S0162-0134(17)30634-7
Knihovny.cz E-resources
- Keywords
- (Arene)ruthenium(II) complexes, DNA binding, Naphthopyran, Vascular-disrupting agents (VDA), Zebrafish,
- MeSH
- HT29 Cells MeSH
- Chorioallantoic Membrane drug effects MeSH
- Cisplatin pharmacology MeSH
- Zebrafish MeSH
- DNA chemistry MeSH
- Coordination Complexes chemistry MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Cell Line, Tumor MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Electrophoretic Mobility Shift Assay MeSH
- Ruthenium chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- calf thymus DNA MeSH Browser
- Cisplatin MeSH
- DNA MeSH
- Coordination Complexes MeSH
- Antineoplastic Agents MeSH
- Ruthenium MeSH
A series of four 2‑amino‑3‑cyano‑4‑(3/4‑pyridyl)‑4H‑benzo[h]chromenes 2a-d and their dichlorido(p‑cymene)ruthenium(II) complexes 3a-d were tested for antiproliferative, vascular-disruptive, anti-angiogenic and DNA-binding activity. The coordination of the 4‑pyridyl‑4H‑naphthopyrans 2 to ruthenium led to complexes with pleiotropic effects. Unlike the free ligands 2a-d, their ruthenium complexes 3a-d showed a significant affinity for DNA as demonstrated by electrophoretic mobility shift assays (EMSA) and ethidium bromide assays. Binding of 3a-d to calf thymus DNA proceeded about 10-times faster compared with cisplatin. Treatment of HT-29 colon carcinoma, 518A2 melanoma and MCF-7Topo breast cancer cells with 3a and 3b caused an accumulation of cells in the G2/M phase and an increase of the fraction of mitotic cells in the case of HT-29, due to alterations of the microtubule cytoskeleton as shown by immunofluorescence staining. Complexes 3b-c showed a dual effect on the vascular system. They suppressed angiogenesis in zebrafish embryos and they destroyed the vasculature of the chorioallantoic membrane (CAM) in fertilized chicken eggs. They also inhibited the vasculogenic mimicry, typical of U-87 glioblastoma cells in tube formation assays.
Department of Chemistry University of Bayreuth Universitaetsstrasse 30 95440 Bayreuth Germany
Developmental Biology University of Bayreuth Universitaetsstrasse 30 95440 Bayreuth Germany
Institute of Biophysics Academy of Sciences of the Czech Republic CZ 61265 Brno Czech Republic
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