Comparative Study of the Inclusion Complexation of Pizotifen and Ketotifen with Native and Modified Cyclodextrins (original) (raw)
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Praziquantel (PZQ) is a broadly effective anthelminthic drug available for human and veterinary use, being the drug of choice for the treatment of all forms of schistosomiasis. Nevertheless, large doses are required in order to achieve adequate concentrations at the target site due to the poor solubility of PZQ and its significant first pass metabolism. To improve it, avoiding efficiency loss, we have designed a controlled-release system, in which PZQ was encapsulated in -cyclodextrin ( -CD). The inclusion complexes between PZQ/ -CD were studied at two different stoichiometries 1:1 and 1:2, through experimental and theoretical analysis. Molecular modeling calculations were used to foresee the better stoichiometry of the complex formed as well as the possible orientations of PZQ inside the -CD cavity. The complexes prepared were analyzed through 1H two-dimensional nuclear magnetic resonance (1H 2D-NMR) experiments, which provide (evidences) for the 1:1 complexation of PZQ/ -CD. 1H 2D-NMR also revealed details of PZQ/ -CD molecular interaction, in which the isoquinoline ring of praziquantel is located inside the -CD cavity. Finally, phase-solubility diagrams revealed a five-fold increase in praziquantel water solubility upon addition of increasing -CD concentrations up to 16 mM, corresponding to the solubility of -CD itself. The solubilization profile is consistent with 1:1 stoichiometry of the PZQ/ -CD complex while the solubilization effect will certainly increase the pharmacological activity of praziquantel.
Interaction Energy Analysis for Drug-Cyclodextrin Inclusion Complexes in Aqueous Solutions
Journal of Applied Solution Chemistry and Modeling, 2012
It is vital to elucidate the role of asymmetric intermolecular interactions resulting from the stereospecific structures of molecules in order to understand the mechanisms of chemical and biochemical reactions such as enzymesubstrate reactions, antigen-antibody reactions, etc. In order to reveal the mechanism of the inclusion phenomenon for β-cyclodextrin (CD)-ampicillin complexes and β-CD-ibuprofen complexes, binding free energies were determined using molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) analysis. To clarify the details of the interaction energies of these complexes, pair interaction energy decomposition analysis (PIEDA) was carried out. The direction of inclusion of drugs into β-CD cavities was clarified on the basis of results obtained using the above-mentioned methods.
Beilstein journal of organic chemistry, 2017
Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1/β-CD and 2/β-CD complexes, with the aromatic ring system entering the cavity from the large rim of the cyclodextrin and the alkylammonium chain protruding out of the cavity and facing the secondary OH rim. These features matched those found in the molecular dynamics (MD) simulations in solution and in the solid state from single-crystal X-ray diffraction of 1/β-CD and 2/β-CD complexes. The latter complex was found in a single conformation in the solid state, whilst the MD simulations in explicit water reproduced the conformational transitions observed experimentally for the free molecule.