Anthraquinone–chalcone hybrids: Synthesis, preliminary antiproliferative evaluation and DNA-interaction studies

•New anthraquinone–chalcone hybrids were prepared.•All compounds showed high cytotoxicity and good selectivity in HeLa cells.•Western blot indicated induction of caspase-dependent apoptosis in HeLa cells.•Three leading derivatives exhibited CT-DNA binding activity.

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 × 103 M−1, 1.36 × 103 M−1and 2.51 × 103 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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