Side Chain-Dependent Binding of bis-Naphthalimide Self-Assembled Nanoparticles to G-Quadruplex DNA for Potential Anticancer Therapy

Novel bis-naphthalimide (NI)-based molecules composed of a space linker (bis-NI1, bis-NI2: phenyl dialkyne/ bis-NI3, bis-NI4: triazole/ bis-NI5, bis-NI6: alkyne) with the distinctive side chain of 2,6-diisopropylaniline or 2,4,6-trimethylaniline were designed and synthesized as nanoparticles (NPs) that bind to G-quadruplex (G4) DNA. The supramolecular assemblies of the bis-NIs were found to form isolated spheres (bis-NI1, bis-NI3), dumbbells with or without a cylindrical bridge (bis-NI2, bis-NI4), and needle-like structures (bis-NI6). The side chain of 2,4,6-trimethylaniline is suggested to play a key role in the self-assembly of the bridge-connected shape such as dumbbells or needle in bis-NIs with three different space linkers. The small sphere shaped NP formed by bis-NI1 displayed both intercalation and groove binding to G4-DNAs, while a larger sphere shaped NP of bis-NI3 represented binding to the G4-DNA groove. The dumbbells of bis-NI2 showed both intercalation and groove binding to G4-DNAs, whereas ...