PURPOSE: Acyclic nucleoside phosphonates possess unique antiviral and antineoplastic activities; however, their polar phosphonate moiety is associated with low ability to cross biological membranes. We explored the potential of transdermal and topical delivery of 2,6-diaminopurine derivative cPr-PMEDAP. METHODS: In vitro diffusion of cPr-PMEDAP was investigated using formulations at different pH and concentration and with permeation enhancer through porcine and human skin. RESULTS: Ability of 0.1-5% cPr-PMEDAP to cross human skin barrier was very low with flux values ~40 ng/cm(2)/h, the majority of compound found in the stratum corneum. The highest permeation rates were found at pH 6; increased donor concentration had no influence. The permeation enhancer dodecyl 6-dimethylaminohexanoate (DDAK, 1%) increased flux of cPr-PMEDAP (up to 61 times) and its concentration in nucleated epidermis (up to ~0.5 mg of cPr-PMEDAP/g of the tissue). No deamination of cPr-PMEDAP into PMEG occurred during permeation studies, but N-dealkylation into PMEDAP mediated by skin microflora was observed. CONCLUSIONS: Transdermal or topical application of cPr-PMEDAP enabled by the permeation enhancer DDAK may provide an attractive alternative route of administration of this potent antitumor and antiviral compound.

• MeSH
• adenin aplikace a dávkování   MeSH
• antitumorózní látky aplikace a dávkování   MeSH
• antivirové látky aplikace a dávkování   MeSH
• aplikace kožní MeSH
• dimethylaminy MeSH
• dodekanol MeSH
• kapronáty metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• kůže metabolismus   MeSH
• lidé MeSH
• methylaminy metabolismus   MeSH
• organofosfonáty aplikace a dávkování   MeSH
• permeabilita MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenin MeSH
• antitumorózní látky MeSH
• antivirové látky MeSH
• dimethylaminy MeSH
• dodecyl 6-(dimethylamino)hexanoate MeSH Prohlížeč
• dodekanol MeSH
• kapronáty MeSH
• methylaminy MeSH
• N(6)-cyclopropyl-9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine MeSH Prohlížeč
• organofosfonáty MeSH

2-Amino-4,6-bis[(phosphonomethoxy)alkoxy]pyrimidines bearing two equal or different achiral or chiral phosphonoalkoxy chains have been prepared either by aromatic nucleophilic substitution of 2-amino-4,6-dichloropyrimidine or by alkylation of 4,6-dihydroxy-2-(methylsulfanyl)pyrimidine with appropriate phosphonate-bearing building block. Alkylation of 4,6-dihydroxy-2-(methylsulfanyl)pyrimidine proved to be the method of choice for efficient preparation of variety of bisphosphonates. The enantiomeric purity of selected compounds was determined by capillary electrophoresis. Antiviral activity of bisphosphonates is discussed.

• MeSH
• alkylace MeSH
• antivirové látky chemická syntéza   chemie   farmakologie   MeSH
• bisfosfonáty chemická syntéza   chemie   farmakologie   MeSH
• elektroforéza kapilární MeSH
• HeLa buňky MeSH
• HL-60 buňky MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• molekulární struktura MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nukleosidy chemie   MeSH
• proliferace buněk účinky léků   MeSH
• pyrimidiny chemická syntéza   chemie   farmakologie   MeSH
• stereoizomerie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antivirové látky MeSH
• bisfosfonáty MeSH
• nukleosidy MeSH
• pyrimidiny MeSH