Synthesis, characterization, biological studies (DNA binding, cleavage, antibacterial and topoisomerase I) and molecular docking of copper(II) benzimidazole complexes

To explore the therapeutic potential of copper-based benzimidazole complexes, tetranuclear Cu(II) complex 1 and dinuclear ternary amino acid complexes 2 and 3 {L-trp and L-val, respectively} were synthesized and thoroughly characterized. In vitro DNA binding studies of complexes 1–3 were carried out employing UV–vis titrations, fluorescence, circular dichroic and viscosity measurements which revealed that the complexes 1–3 bind to CT DNA preferably via groove binding. Complex 1 cleaved pBR322 DNA via hydrolytic pathway (validated by T4 DNA ligase assay), accessible to major groove while 2 followed oxidative mechanism, binding to minor groove of DNA double helix; binding events were further validated by molecular docking studies. Additionally, the complexes 1 and 2 exhibit high Topo-I inhibitory activity at different concentrations. The complexes 1–3 were evaluated for antibacterial activity against Escherichia coli and Staphylococcus aureus, and 2 was found to be most effective against Gram-positive bacteria.

Molecular docking techniques were performed to elucidate the molecular recognition of multinuclear copper(II) complexes of benzimidazole scaffold towards the major/minor groove of DNA as Topo-I inhibitors.Figure optionsDownload as PowerPoint slideHighlights
► Tetranuclear Cu(II) complex, 1 and dinuclear amino acid ternary benzimidazole complexes 2 and 3.
► In vitro DNA binding studies with CT DNA.
► Complex 1 cleaved pBR322 DNA via hydrolytic mechanism (validated by T4 DNA ligase).
► Complexes show high inhibition activity against Topo-I.
► Validation by molecular docking studies.