title: Anthraquinone-chalcone hybrids: synthesis, preliminary antiproliferative evaluation and DNA-interaction studies.
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.
authors.affiliation: Faculty of Science, Department of Chemistry, University of Kragujevac, R. Domanovica 12, 34000 Kragujevac, Serbia.
authors.forename: Violeta
authors.initials: V
authors.lastname: Marković
authors.affiliation: Faculty of Science, Department of Chemistry, University of Kragujevac, R. Domanovica 12, 34000 Kragujevac, Serbia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Debeljak
authors.affiliation: Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stanojković
authors.affiliation: Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
authors.forename: Branka
authors.initials: B
authors.lastname: Kolundžija
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia.
authors.forename: Dušan
authors.initials: D
authors.lastname: Sladić
authors.affiliation: Institute for Chemistry, Technology and Metallurgy, Department of Chemistry, Njegoševa 12, 11000 Belgrade, Serbia.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Vujčić
authors.affiliation: Institute for Chemistry, Technology and Metallurgy, Department of Chemistry, Njegoševa 12, 11000 Belgrade, Serbia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Janović
authors.affiliation: Institute for Biological Research "Siniša Stanković", Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Tanić
authors.affiliation: Institute for Biological Research "Siniša Stanković", Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Milka
authors.initials: M
authors.lastname: Perović
authors.affiliation: Institute for Biological Research "Siniša Stanković", Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Tešić
authors.affiliation: Institute of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Dr Subotića 13, 11000 Belgrade, Serbia.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Antić
authors.affiliation: Faculty of Science, Department of Chemistry, University of Kragujevac, R. Domanovica 12, 34000 Kragujevac, Serbia. Electronic address: mjoksovic@kg.ac.rs.
authors.forename: Milan D
authors.initials: MD
authors.lastname: Joksović
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D047188:Chalcones; D004247:DNA; C427203:calf thymus DNA
keywords: Anthraquinone; Apoptosis; Chalcone; Cytotoxicity; DNA study