Synthesis of naphthalimide-phenanthro[9,10-d]imidazole derivatives: In vitro evaluation, binding interaction with DNA and topoisomerase inhibition

A series of naphthalimide based phenanthro[9,10-d]imidazole derivatives has been synthesized and screen in vitro biological activity for human cancer cell lines representing nine different cancer types. The most potent derivative, 1-ethylpiperazine substituted at naphthalimide (16) was further studied to evaluate the interaction with ct-DNA and topoisomerase inhibition. [Display omitted] •A series of naphthalimide and phenanthro[9,10-d]imidazole derivatives has been synthesized.•Fourteen compounds were studied for their In vitro antitumor activity.•Binding mechanism of derivative 16 was studied with ct-DNA.•Compound 16 was induced apoptosis and inhibits human topoisomerase-IIα. The synthesis and characterization of a series of naphthalimide and phenanthro[9,10-d]imidazole conjugate is described. These compounds are evaluated in vitro for their cytotoxicity towards 60 human cancer cell lines. Derivative 16 shows excellent cytotoxic activity against these cancer cell lines with the range of growth inhibition from −55.78 to 94.53. The most potent derivative (ethylpiperazine, 16) is further studied to evaluate the interaction with ct-DNA using absorption and emission spectroscopy as well as DNA viscosity measurement. The DNA binding studies indicate that compound 16 is significantly interacted with DNA through groove binding having binding constant value of 7.81 × 104 M−1 alongwith partial intercalation between the base pairs of DNA strands. Further, topoisomerase inhibition study suggests that compound 16 is induced apoptosis and inhibits human topoisomerase (Topo-IIα) as a possible intracellular target. Molecular docking study of compound 16 with ct-DNA shows good docking score.