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1.
J Pharm Sci ; 85(2): 200-5, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8683449

RESUMO

Crucial conditions for the pharmacological use of active compounds are their ability to cross the biological barriers and reach their intracellular target. In the case of two antiviral pyridopurine derivatives, 1 and 2, this included essentially the membranes and the nucleic acids. Thus the interactions of 1 and 2 with model membranes and oligonucleotides were studied using NMR spectroscopy. It was found that these hydrophobic molecules can be incorporated into the model membranes at the terminal methyl group level, inducing dynamic perturbations in the bilayer. In the presence of the synthetic oligonucleotide ACATGT, both molecules can intercalate aspecifically in AT and GC systems. Inclusion complexes of 1 and 2 beta-cyclodextrins with a 1:1 stoichiometry, were also prepared. This led to to propose two galenic forms 1 and 2, i.e. included in phospholipid vesicles in the form of a beta-cyclodextrin complex


Assuntos
Aminas/química , Ciclodextrinas/química , Preparações Farmacêuticas/química , Dimiristoilfosfatidilcolina/química , Alimentos , Espectroscopia de Ressonância Magnética
2.
Boll Chim Farm ; 135(3): 192-8, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8974421

RESUMO

Three potentially antiviral imidazo[1,2-a]pyridine derivatives of increasing hydrophilicity were tested in their interactions with model membranes and synthetic oligonucleotides. It was shown that the most hydrophobic derivative [1], located in the depth of the bilayer only induces minor membrane damages. The molecule [2], only poorly hydrophobic, integrates also the bilayer in the medium part of the chains while the most hydrophilic [3] exhibits fluidizing and slightly detergent properties. In the presence of synthetic oligonucleotide ACATGT no intercallation of the three derivatives was evidenced. By considering their antiviral activity in the absence of evident mitogenic properties, another mechanism of action was proposed.


Assuntos
Antivirais/química , Imidazóis/química , Piridinas/química , Bicamadas Lipídicas/química , Espectroscopia de Ressonância Magnética , Membranas Artificiais , Oligonucleotídeos/química
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