Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle
Our previous studies on antiproliferative properties of genistein derivatives substituted at C7 hydroxyl group of the ring A revealed some compounds with antimitotic properties. The aim of this work was to synthesize their analogues substituted at the 4′-position of the ring B in genistein and to de...
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Wiley
2013-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2013/191563 |
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| author | A. Byczek J. Zawisza-Puchalka A. Gruca K. Papaj G. Grynkiewicz M. Rusin W. Szeja A. Rusin |
| author_facet | A. Byczek J. Zawisza-Puchalka A. Gruca K. Papaj G. Grynkiewicz M. Rusin W. Szeja A. Rusin |
| author_sort | A. Byczek |
| collection | DOAJ |
| description | Our previous studies on antiproliferative properties of genistein derivatives substituted at C7 hydroxyl group of the ring A revealed some compounds with antimitotic properties. The aim of this work was to synthesize their analogues substituted at the 4′-position of the ring B in genistein and to define their antiproliferative mechanism of action in selected cancer cell lines in vitro. C4′-substituted glycoconjugates were obtained in a three-step procedure: (1) alkylation with an ω-bromoester; (2) deacylation; (3) Ferrier-type rearrangement glycosylation with acylated glycals. Biological effects including antiproliferative effects of the compounds, cell cycle, DNA lesions (ATM activation, H2A.X phosphorylation, and micronuclei formation), and autophagy were studied in human cancer cell lines. Some of the tested derivatives potently inhibited cell proliferation. The presence of a substituent at the 4′-position of the ring B in genistein correlated to a p53-independent G1 cell-cycle arrest. The derivatives substituted at C4′ did not induce DNA lesions and appeared to be nongenotoxic. The tested compounds induced autophagy and caused remarkable decrease of cell volume. |
| format | Article |
| id | doaj-art-a9acd240a18d4707b4f09cf46333f90a |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-a9acd240a18d4707b4f09cf46333f90a2025-08-20T03:39:10ZengWileyJournal of Chemistry2090-90632090-90712013-01-01201310.1155/2013/191563191563Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell CycleA. Byczek0J. Zawisza-Puchalka1A. Gruca2K. Papaj3G. Grynkiewicz4M. Rusin5W. Szeja6A. Rusin7Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze AK 15, 44-100 Gliwice, PolandDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, PolandDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, PolandDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, PolandPharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, PolandCenter for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze AK 15, 44-100 Gliwice, PolandDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, PolandCenter for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze AK 15, 44-100 Gliwice, PolandOur previous studies on antiproliferative properties of genistein derivatives substituted at C7 hydroxyl group of the ring A revealed some compounds with antimitotic properties. The aim of this work was to synthesize their analogues substituted at the 4′-position of the ring B in genistein and to define their antiproliferative mechanism of action in selected cancer cell lines in vitro. C4′-substituted glycoconjugates were obtained in a three-step procedure: (1) alkylation with an ω-bromoester; (2) deacylation; (3) Ferrier-type rearrangement glycosylation with acylated glycals. Biological effects including antiproliferative effects of the compounds, cell cycle, DNA lesions (ATM activation, H2A.X phosphorylation, and micronuclei formation), and autophagy were studied in human cancer cell lines. Some of the tested derivatives potently inhibited cell proliferation. The presence of a substituent at the 4′-position of the ring B in genistein correlated to a p53-independent G1 cell-cycle arrest. The derivatives substituted at C4′ did not induce DNA lesions and appeared to be nongenotoxic. The tested compounds induced autophagy and caused remarkable decrease of cell volume.http://dx.doi.org/10.1155/2013/191563 |
| spellingShingle | A. Byczek J. Zawisza-Puchalka A. Gruca K. Papaj G. Grynkiewicz M. Rusin W. Szeja A. Rusin Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle Journal of Chemistry |
| title | Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle |
| title_full | Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle |
| title_fullStr | Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle |
| title_full_unstemmed | Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle |
| title_short | Genistein Derivatives Regioisomerically Substituted at 7-O- and 4′-O- Have Different Effect on the Cell Cycle |
| title_sort | genistein derivatives regioisomerically substituted at 7 o and 4 o have different effect on the cell cycle |
| url | http://dx.doi.org/10.1155/2013/191563 |
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