Skin penetration/permeation enhancers are compounds that improve (trans)dermal drug delivery. We designed hybrid terpene-amino acid enhancers by conjugating natural terpenes (citronellol, geraniol, nerol, farnesol, linalool, perillyl alcohol, menthol, borneol, carveol) or cinnamyl alcohol with 6-(dimethylamino)hexanoic acid through a biodegradable ester linker. The compounds were screened for their ability to increase the delivery of theophylline and hydrocortisone through and into human skin ex vivo. The citronellyl, bornyl and cinnamyl esters showed exceptional permeation-enhancing properties (enhancement ratios up to 82) while having low cellular toxicities. The barrier function of enhancer-treated skin (assessed by transepidermal water loss and electrical impedance) recovered within 24 h. Infrared spectroscopy suggested that these esters fluidized the stratum corneum lipids. Furthermore, the citronellyl ester increased the epidermal concentration of topically applied cidofovir, which is a potent antiviral and anticancer drug, by 15-fold. In conclusion, citronellyl 6-(dimethylamino)hexanoate is an outstanding enhancer with an advantageous combination of properties, which may improve the delivery of drugs that have a limited ability to cross biological barriers.
- MeSH
- alkoholy chemie farmakologie MeSH
- aplikace kožní MeSH
- buňky 3T3 MeSH
- chemie farmaceutická MeSH
- cidofovir aplikace a dávkování chemie farmakokinetika MeSH
- epidermis účinky léků metabolismus MeSH
- estery chemie farmakologie MeSH
- farmaceutické pomocné látky chemie farmakologie MeSH
- hydrokortison aplikace a dávkování chemie farmakokinetika MeSH
- keratinocyty MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- monoterpeny chemie MeSH
- myši MeSH
- permeabilita účinky léků MeSH
- perspiratio insensibilis účinky léků MeSH
- příprava léků metody MeSH
- terpeny chemie farmakologie MeSH
- testy akutní toxicity MeSH
- theofylin aplikace a dávkování chemie farmakokinetika 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
In solid-phase organic synthesis, Wang resin is traditionally used for the immobilization of acids, alcohols, phenols, and amines. We report the use of Wang resin for the traceless synthesis of ketones via acid-labile enol ethers. We demonstrate the practicality of this synthetic strategy on the solid-phase synthesis of pyrrolidine-2,4-diones, which represent the core structure of several natural products, including tetramic acid. Base-triggered condensation of pyrrolidine-2,4-diones yielded 4-hydroxy-1,1',2',5-tetrahydro-2H,5'H-[3,3'-bipyrrole]-2,5'-diones.
- MeSH
- alkoholy * chemická syntéza chemie MeSH
- aminy chemie MeSH
- ketony * chemická syntéza chemie MeSH
- Publikační typ
- časopisecké články MeSH
Termite colonies are almost always founded by a pair of winged dispersers, in spite of the high costs and low success rates inherent in independent colony foundation. The dispersal flights of imagoes from natal colonies are followed by mate search, mediated by sex-pairing pheromones. Here, we studied the chemistry of sex-pairing pheromones and the related aspects of mate search in winged imagoes of two facultatively parthenogenetic species, Embiratermes neotenicus and Silvestritermes minutus, and an additional species from the same subfamily, Silvestritermes heyeri. All three species are widespread in the Neotropics, including the rainforests of French Guiana. After the dispersal flight and spontaneous loss of wings, females expose their hypertrophied tergal glands situated under abdominal tergites VIII - X. The females are attractive to males and, upon direct contact, the two sexes form characteristic tandems. Chemical analyses indicated that the females secrete species-specific combinations of unbranched, unsaturated C12 primary alcohols from the tergal glands, (3Z,6Z,8E)-dodeca-3,6,8-trien-1-ol (approx. 200 pg per female) and (3Z)-dodec-3-enol (185 pg) in E. neotenicus, (3Z,6Z)-dodeca-3,6-dien-1-ol (3500 pg) in S. heyeri, and (3Z,6Z)-dodeca-3,6-dien-1-ol (300 pg) and (3Z)-dodec-3-enol (50 pg) in S. minutus. (3Z,6Z,8E)-Dodeca-3,6,8-trien-1-ol and (3Z,6Z)-dodeca-3,6-dien-1-ol act as major pheromone components in the respective species and mimic the function of female tergal gland extracts in electrophysiological and behavioral experiments. Biologically relevant amounts of the third compound, (3Z)-dodec-3-enol, elicited non-significant reactions in males of E. neotenicus and S. minutus, and slight synergistic effects in males of S. minutus when tested in combination with the major component.
- MeSH
- alkoholy chemie izolace a purifikace MeSH
- druhová specificita MeSH
- exokrinní žlázy metabolismus patologie MeSH
- Isoptera fyziologie MeSH
- mikroextrakce na pevné fázi MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody MeSH
- sexuální chování zvířat fyziologie MeSH
- sexuální lákadla analýza chemie izolace a purifikace MeSH
- stereoizomerie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
17β-O-Hemisuccinates of typical representatives of Anabolic-Androgenic Steroids, 17β-hydroxy-17-methylandrostan-4-en-3-one, 17β-hydroxy-17-methyl-2-oxa-5α-androstan-3-one, 17β-hydroxy-17-methyl-5α-androstano-[3,2-c]pyrazole, were prepared. Several methods for the hemisuccinate preparation were tested. The indirect method using 1-ethyl-3-(dimethylaminopropyl)carbodiimide coupling reagent to form an ester bond of steroid with 2-(trimethylsilyl)ethyl hydrogen butanedioate was finally applied. Using the selectively removable protecting group, the desired hemisuccinates of steroids bearing tertiary alcohol group were obtained.
N-Benzyl-2-nitrobenzenesulfonamides underwent base-mediated intramolecular arylation at the benzyl sp(3) carbon to yield benzhydrylamines. The presence of electron withdrawing groups on the aromatic ring of the benzyl group was required to facilitate the C-arylation. Unsymmetrically substituted benzhydrylamines are advanced intermediates toward nitrogenous heterocycles, as exemplified in the syntheses of indazole oxides and quinazolines.
- MeSH
- alkoholy chemie MeSH
- benzhydrylové sloučeniny chemie MeSH
- benzylové sloučeniny chemie MeSH
- chinazoliny chemická syntéza MeSH
- heterocyklické sloučeniny chemická syntéza MeSH
- indazoly chemická syntéza MeSH
- indikátory a reagencie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Clusters of a solute and a few solvent molecules obtained from molecular dynamics (MD) are a powerful tool to study solvation effects by advanced quantum chemical (QC) methods. For spectroscopic properties strongly dependent on the solvation, however, a large number of clusters are needed for a good convergence. In this work, a parallel variable selection (PVS) method is proposed that in some cases efficiently reduces the number of clusters needed for the averaging. The mass, charge, or atomic density MD distributions are used as a secondary variable to preselect the most probable cluster geometries used for averaging of solute spectral properties. When applied to nuclear magnetic resonance chemical shift of a model alcohol, the method allowed one to significantly reduce the total computational time, by a factor of 10. Even larger savings were achieved for the modeling of Raman and Raman optical activity spectra of (S)-lactamide molecule dissolved in water. The results thus suggest that the PVS method can be generally used for simulations of spectroscopic properties of solvated molecules and makes multiscale MD/QC computations more affordable.
The subjects of this article are cyclic alcohols with hydroxyl group bound directly to one carbon of the three- up to six-membered ring. They are thus predominantly secondary alcohols. These are substances frequently used as synthons in organic synthesis and many of them are important raw materials of chemical industry, such as cyclohexanol. Some cyclic alcohols were also found in nature, the bulk of them belong to the category of monoterpene substances. Many of them have biological activity, which is also discussed in this article.
- MeSH
- alkoholy * chemie klasifikace MeSH
- bornany chemie MeSH
- cyklobutany klasifikace MeSH
- cyklohexany chemie MeSH
- ethery cyklické * chemie klasifikace MeSH
- inositol analogy a deriváty chemie MeSH
- lidé MeSH
- menthol chemie MeSH
- monoterpeny chemie MeSH
- pojmy organické chemie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Chlorosomes from green photosynthetic bacteria are large photosynthetic antennae containing self-assembling aggregates of bacteriochlorophyll c, d, or e. The pigments within chlorosomes are organized in curved lamellar structures. Aggregates with similar optical properties can be prepared in vitro, both in polar as well as non-polar solvents. In order to gain insight into their structure we examined hexane-induced aggregates of purified bacteriochlorophyll c by X-ray scattering. The bacteriochlorophyll c aggregates exhibit scattering features that are virtually identical to those of native chlorosomes demonstrating that the self-assembly of these pigments is fully encoded in their chemical structure. Thus, the hexane-induced aggregates constitute an excellent model to study the effects of chemical structure on assembly. Using bacteriochlorophyllides transesterified with different alcohols we have established a linear relationship between the esterifying alcohol length and the lamellar spacing. The results provide a structural basis for lamellar spacing variability observed for native chlorosomes from different species. A plausible physiological role of this variability is discussed. The X-ray scattering also confirmed the assignments of peaks, which arise from the crystalline baseplate in the native chlorosomes.
- MeSH
- alkoholy chemie MeSH
- anizotropie MeSH
- bakteriochlorofyly chemie metabolismus MeSH
- buněčné struktury metabolismus MeSH
- Chlorobium metabolismus MeSH
- esterifikace MeSH
- hexany chemie MeSH
- kvarterní struktura proteinů MeSH
- radiační rozptyl MeSH
- rentgenové záření MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In order to investigate the effect of branching and cyclization in the hydrophobic part of skin permeation enhancers, 17 novel branched-chain and cyclic 6-aminohexanoic acid esters were prepared. Their permeation enhancing activity was evaluated in vitro using human skin and theophylline as a model drug, and compared to that of the corresponding linear-chain analogues. The results showed that chain branching and cyclization has a negative influence on the enhancing activity of 6-aminohexanoates. For example, the enhancement ratios (ERs) of dodecan-1-yl, dodecan-2-yl, dodecan-4-yl, and cyclododecyl ester were 39.7, 29.3, 3.1, and 2.2, respectively. No significant change in the optimum length of the chain was observed. Dodecan-2-yl 6-aminohexanoate, the most active branched derivative, still maintains a remarkable enhancing activity (ER 29.3). Presumably, the relatively small degree of branching of these molecules does not prevent them from interacting with the lipid components of the stratum corneum. However, a higher degree of branching, cyclization of the chain, and presence of an aromatic ring resulted in a loss of activity. (c) 2005 Wiley-Liss, Inc.
- MeSH
- alkoholy chemie MeSH
- estery farmakologie chemie MeSH
- financování vládou MeSH
- kožní absorpce účinky léků MeSH
- kyselina 6-aminokapronová analogy a deriváty farmakologie chemie MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- techniky in vitro MeSH
