Abstract |
Novel anthraquinone based chalcone compounds were synthesized starting from 1-acetylanthraquinone in a Claisen-Schmidt reaction and evaluated for their anticancer potential against three human cancer cell lines. Compounds 4a, 4b and 4j showed promising activity in inhibition of HeLa cells with IC50 values ranging from 2.36 to 2.73 μM and low cytotoxicity against healthy MRC-5 cell lines. The effects that compounds produces on the cell cycle were investigated by flow cytometry. It was found that 4a, 4b and 4j cause the accumulation of cells in the S and G2/M phases in a dose-dependent manner and induce caspase-dependent apoptosis. All of three compounds exhibit calf thymus DNA-binding activity. The determined binding constants by absorption titrations (2.65 × 10(3) M(-1), 1.36 × 10(3) M(-1)and 2.51 × 10(3) M(-1) of 4a/CT- DNA, 4b/CT- DNA and 4j/CT- DNA, respectively) together with fluorescence displacement analysis designate 4a, 4b and 4j as strong minor groove binders, but no cleavage of plasmid DNA was observed.
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Authors | Violeta Marković, Nevena Debeljak, Tatjana Stanojković, Branka Kolundžija, Dušan Sladić, Miroslava Vujčić, Barbara Janović, Nikola Tanić, Milka Perović, Vesna Tešić, Jadranka Antić, Milan D Joksović |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 89
Pg. 401-10
(Jan 07 2015)
ISSN: 1768-3254 [Electronic] France |
PMID | 25462255
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Anthraquinones
- Antineoplastic Agents
- Chalcones
- DNA
- calf thymus DNA
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Topics |
- Anthraquinones
(chemical synthesis, chemistry, pharmacology)
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Apoptosis
(drug effects)
- Binding Sites
- Cell Cycle
(drug effects)
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Chalcones
(chemical synthesis, chemistry, pharmacology)
- DNA
(chemistry)
- Fibroblasts
(drug effects, pathology)
- HeLa Cells
- Humans
- Molecular Structure
- Structure-Activity Relationship
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