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

Abstract

A new series of different naphthalimide-benzothiazole/cinnamide derivatives were designed, synthesized and tested for their <i>in vitro</i> cytotoxicity on selected human cancer cell lines. Among them, derivatives <b>4a</b> and <b>4b</b> with the 6-aminobenzothiazole ring and <b>5g</b> 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 <b>4a</b> and <b>4b</b> were also found to inhibit DNA topoisomerase-II.