Skin penetration enhancers are compounds used to facilitate the transdermal delivery of drugs that are otherwise not sufficiently permeable. Through a synthetic route implementing two series of esters, we generated transdermal penetration enhancers by a multi-step reaction with substituted 6-aminohexanoic acid. We present the synthesis of all newly prepared compounds here with structural confirmation accomplished by (1)H NMR, (13)C NMR, IR and mass spectroscopy (MS). The lipophilicity (logk) of all compounds was determined via RP-HPLC and their hydrophobicity (logP/ClogP) was also calculated using two commercially available programs. Ab initio calculations of geometry and molecular dynamic simulations were employed to investigate the 3-dimensional structures of selected compounds. The transdermal penetration-enhancing activity of all the synthesized esters were examined in vitro and demonstrated higher enhancement ratios than oleic acid. Compounds 2e (C(10) ester chain) and 2f (C(11) ester chain) exhibited the highest enhancement ratios. It can be concluded that the series non-substituted at the C((2)) position by a ω-lactam ring showed significantly higher activity than those with azepan-2-one. None of the prepared compounds penetrated through the skin. All of the investigated agents demonstrated minimal anti-proliferative activity using the SK-N-MC neuroepithelioma cell line (IC(50)>6.25μM), suggesting these analogs would have a low cytotoxic profile when administered in vivo as chemical penetration enhancers. The correlation between the chemical structure of the studied compounds and their lipophilicity is discussed in regards to transdermal penetration-enhancing activity.

• MeSH
• antitumorózní látky chemická syntéza   chemie   farmakologie   MeSH
• aplikace lokální MeSH
• hydrofobní a hydrofilní interakce MeSH
• kapronáty chemická syntéza   chemie   farmakologie   MeSH
• kožní absorpce MeSH
• kůže účinky léků   MeSH
• kyselina 6-aminokapronová chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• prasata MeSH
• pyrrolidiny chemická syntéza   chemie   farmakologie   MeSH
• simulace molekulární dynamiky MeSH
• stereoizomerie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• decyl-6-(2,5-dioxopyrrolidin-1-yl)hexanoate MeSH Prohlížeč
• kapronáty MeSH
• kyselina 6-aminokapronová MeSH
• pyrrolidiny MeSH
• undecyl-6-(2,5-dioxopyrrolidin-1-yl)hexanoate MeSH Prohlížeč

The conformation of a permeation enhancer, given their mechanism of action, could influence its enhancing properties, since the stratum corneum components form essentially a chiral environment. The racemate and both enantiomers of 6-aminohexanoic acid 2-octylester as model enhancers with one chiral center were synthesized and their ability to enhance in vitro theophylline permeation through human skin was tested. The MTMT concept could not be applied in this study (the melting points of the substances were lower than 20 masculine C) and we observed no significant difference in enhancement ratios (ERs) of racemic 6-aminohexanoic acid 2-octylester and that of each enantiomer. However, differences in permeation rates between enantiomers and their racemates do not have to be related to stereoselective interactions, since they may also be explained by differences in physicochemical properties. The study also showed that there was no difference in the permeation enhancement ability between the (R)-(-) and (S)-(+) isomers of 6-aminohexanoic acid 2-octylester (the ERs were 2.72+/-0.42 and 2.79+/-0.60 for (R) and (S) enantiomers, respectively), suggesting that the enhancing properties of the compounds are not dependent on their spatial arrangement. Although stereoselective interactions between an enhancer and stratum corneum components may exist, they seem not to be important for the enhancer action.

• MeSH
• aminokapronáty MeSH
• analýza rozptylu MeSH
• kapronáty farmakologie   MeSH
• kůže metabolismus   MeSH
• lidé MeSH
• permeabilita účinky léků   MeSH
• senioři MeSH
• stereoizomerie MeSH
• theofylin farmakokinetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 6-aminohexanoic acid 2-octyl ester MeSH Prohlížeč
• aminokapronáty MeSH
• kapronáty MeSH
• theofylin MeSH

• MeSH
• aminokapronáty farmakologie   MeSH
• dopamin metabolismus   MeSH
• inbrední kmeny potkanů MeSH
• kapronáty farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyselina 6-aminokapronová farmakologie   MeSH
• mozek účinky léků   metabolismus   MeSH
• noradrenalin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokapronáty MeSH
• dopamin MeSH
• hexanoic acid MeSH Prohlížeč
• kapronáty MeSH
• kyselina 6-aminokapronová MeSH
• noradrenalin MeSH