betadex and coumarin-6

We report in this paper that the binding of coumarin 6 (C6) to DNA can be tuned by complexing it with host structures, viz. β-cyclodextrin (β-CD) and C-hexylpyrogallol-4-arene (C-HPA). Because host molecules are used as carriers of small molecules onto target sites, the exposed part of the guest molecule needs to be found out, and the relationship between the host : guest ratio and the mode of binding with the target macromolecule, that is, the DNA needs to be analyzed, in order to comprehend the preferred binding moiety and tune the binding. In this paper, the formation of the inclusion complex of C6 with β-CD and with C-HPA is studied by UV-visible, fluorescence, 2D rotating-frame nuclear Overhauser effect correlation spectroscopy and diffusion-ordered spectroscopy nuclear magnetic resonance spectra and molecular modeling. C6 forms a 1:1 complex with β-CD and a 1:2 complex with C-HPA. The studies on the protonation of C6 in the presence and the absence of the host molecules suggest that the chromone part of C6 is outside the β-CD molecule, whereas it is fully covered by C-HPA. The binding of C6 with calf thymus DNA (ctDNA) occurs through intercalation and hydrogen bonding, and the host-guest structures remain intact on binding with ctDNA. The oxygens of the C6 molecules are exposed when inside the host molecules and aid in the hydrogen bonding with DNA.

Topics: Animals; beta-Cyclodextrins; Binding Sites; Cattle; Coumarins; DNA; Hydrogen Bonding; Macromolecular Substances; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Pyrogallol; Thiazoles

Novel polymeric nanoparticles based on a beta-cyclodextrin-poly(4-acryloylmorpholine) mono-conjugate (beta-CD-PACM), a tadpole-shaped polymer in which the beta-CD ring is the hydrophilic head and the PACM chain the amphiphilic tail, were prepared by the solvent injection technique. Acyclovir-loaded nanoparticles were prepared from inclusion complexes of Acyclovir with beta-CD-PACM. Both unloaded and drug-loaded nanoparticles were characterized in terms of particle size distribution, morphology, zeta potential, drug loading and in vitro drug release rate. The antiviral activity of Acyclovir loaded into beta-CD-PACM nanoparticles against two clinical isolates of HSV-1 was evaluated and found to be remarkably superior compared with that of both the free drug and a soluble beta-CD-PACM complex reported in a previous paper. Fluorescent nanoparticles loaded with coumarin 6 were also prepared in order to investigate the nanoparticle cell uptake by confocal laser microscopy. It was found that the nanoparticles are internalized in cells and locate in the perinuclear compartment.

Topics: Acrylamides; Acyclovir; Animals; Antiviral Agents; beta-Cyclodextrins; Cell Membrane Permeability; Cell Survival; Chlorocebus aethiops; Coumarins; Drug Carriers; Herpesvirus 1, Human; Morpholines; Nanoparticles; Particle Size; Polymers; Thiazoles; Vero Cells