DNA-binding affinity and anticancer activity of β-carboline–chalcone conjugates as potential DNA intercalators: Molecular modelling and synthesis

• A series of β-carboline–chalcone conjugates have been synthesized.
• Cytotoxicity tested on HeLa, HT-29, A-549, PC-3 and B-16 cell lines.
• DNA-binding affinity was evaluated by thermal denaturation studies.
• Compounds showed significant elevation in ΔTm and potent in vitro cytotoxicity.
• Fluorescence titration and molecular dynamics established DNA intercalation.

A new series of DNA-interactive β-carboline–chalcone conjugates have been synthesized and evaluated for their in vitro cytotoxicity and DNA-binding affinity. It has been observed that most of these new hybrids have shown potent cytotoxic activities on A-549 (lung adenocarcinoma) cell lines with IC50 values lower than 10 μM. The hybrid 7b is more effective against some of the selected cancer cell lines with IC50 values less than 50 μM. In addition, compounds 7e, 7k, 7p–u has displayed significant elevation in ΔTm of DNA in comparison to Adriamycin, suggesting significant interaction and remarkable DNA stabilization. The DNA intercalation of these new hybrids has been investigated by fluorescence titration, DNA viscosity measurements, molecular docking as well as molecular dynamics and the results are in agreement with the thermal denaturation studies.

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