Side-Chain-Dependent Binding of bis-Naphthalimide Self-Assembled Nanoparticles to G‑Quadruplex DNA for Potential Anticancer Therapy
journal contributionposted on 04.02.2020 by Goutam Kulsi, Annie Agnes Suganya Samson, Baskaran Purushothaman, Joon Myong Song
Any type of content formally published in an academic journal, usually following a peer-review process.
Novel bis-naphthalimide (NI)-based molecules composed of space linkers of phenyl dialkyne (bis-NI1 and bis-NI2), triazole (bis-NI3 and bis-NI4), and alkyne (bis-NI5 and bis-NI6) 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 the dumbbells of bis-NI4 represented binding to the G4-DNA groove. The needle-shaped bis-NI6 exhibited both intercalation and groove binding to G4-DNAs. Different morphologies of self-assembled bis-NIs provided different IC50 values. Furthermore, bis-NI1, bis-NI4, and bis-NI6 induced cell cycle arrest (G1/S phase) and apoptosis in cancer cells. This suggests bis-NI1, bis-NI4, and bis-NI6 are potential anticancer agents.