Affiliation: Department of Chemistry, National University of Singapore, Singapore 117543.
A series of naphthalene diimide (ND)-based mono-, bis-, and tris-intercalators are synthesized and evaluated for their anticancer activities. All compounds show anticancer activities in the micromolar range. Among them the bis-intercalator is the most promising. Experimental results indicate that (i) target compounds intercalate DNA and (ii) the bis-intercalator with the optimal linker shows considerably more affinity to DNA than corresponding mono-and tris-intercalators. Spectroscopic measurements indicate that the ND groups bind to the double-stranded DNA (ds-DNA) in a classical threading intercalation mode, while the cationic linker reinforces the intercalation via electrostatic interaction with ds-DNA. In vitro cytotoxicity of the bis-intercalator towards a number of cancer cells, such as C6, HeLa, and MDA-435S, is tested and compared to that of normal cells. Attractive anticancer activity is observed with the bisintercalator, which provides a new lead in the anticancer drug design strategy.