Design and synthesis of DNA-intercalative naphthalimide-benzothiazole/cinnamide derivatives: cytotoxicity evaluation and topoisomerase-IIα inhibition.

A new series of different naphthalimide-benzothiazole/cinnamide derivatives were designed, synthesized and tested for their in vitro cytotoxicity on selected human cancer cell lines. Among them, derivatives 4a and 4b with the 6-aminobenzothiazole ring and 5g with the cinnamide ring displayed potent cytotoxic activity against colon (IC50: 3.715 and 3.467 μM) and lung cancer (IC50: 4.074 and 3.890 μM) cell lines when compared to amonafide (IC50: 5.459 and 7.762 μM). Later, the DNA binding studies for these selected derivatives (by CD, UV/vis, fluorescence spectroscopy, DNA viscosity, and molecular docking) suggested that these new derivatives significantly intercalate between two strands of DNA. In addition, the most potent derivatives 4a and 4b were also found to inhibit DNA topoisomerase-II.