One pathway for the preparation of enantiomerically pure compounds from prochiral substrates is the use of metal complex catalysis with chiral ligands. Compared to the other frequently used chiral ligands, chiral 2,2'-bipyridines have been underexploited, despite the data indicating that such ligands have considerable potential in synthetic chemistry. One of those is the so-called Bolm's ligand, a compound possessing chiral alcohol moieties in the side chains attached to the 2,2'-bipyridine scaffold. Various metal salts have been used in combination with Bolm's ligand as potent catalysts able to bring about enantioselective alkylations, allylations, conjugate additions, desymmetrization of meso-epoxides, aldol reactions, etc. This review aims to summarize Bolm's ligand applications in the area of enantioselective synthesis over the last three decades since its preparation.
PURPOSE: To study new skin penetration/permeation enhancers based on amphiphilic galactose derivatives. METHODS: Two series of alkyl and alkenyl galactosides were synthesized and evaluated for their enhancing effect on transdermal/topical delivery of theophylline (TH), hydrocortisone (HC) and cidofovir (CDV), reversibility of their effects on transepidermal water loss (TEWL) and skin impedance, interaction with the stratum corneum using infrared spectroscopy, and cytotoxicity on keratinocytes and fibroblasts. RESULTS: Initial evaluation identified 1-(α-D-galactopyranosyl)-(2E)-pentadec-2-ene A15 as a highly potent enhancer - it increased TH and HC flux through human skin 8.5 and 5 times, respectively. Compound A15 increased the epidermal concentration of a potent antiviral CDV 7 times over that reached by control and Span 20 (an established sugar-based enhancer). Infrared spectroscopy of human stratum corneum indicated interaction of A15 with skin barrier lipids but not proteins. These effects of A15 on the skin barrier were reversible (both TEWL and skin impedance returned to baseline values within 24 h after A15 had been removed from skin). In vitro toxicity of A15 on HaCaT keratinocytes and 3T3 fibroblasts was acceptable, with IC50 values over 60 μM. CONCLUSIONS: Galactosyl pentadecene A15 is a potent enhancer with low toxicity and reversible action.
- MeSH
- alkeny aplikace a dávkování chemie MeSH
- aplikace kožní MeSH
- cytosin aplikace a dávkování analogy a deriváty chemie MeSH
- epidermis metabolismus MeSH
- fibroblasty účinky léků metabolismus MeSH
- galaktosa analogy a deriváty chemie MeSH
- galaktosidy aplikace a dávkování chemie MeSH
- hydrokortison aplikace a dávkování chemie MeSH
- keratinocyty účinky léků metabolismus MeSH
- kožní absorpce účinky léků MeSH
- kůže metabolismus MeSH
- lidé MeSH
- lipidy chemie MeSH
- organofosfonáty aplikace a dávkování chemie MeSH
- permeabilita MeSH
- theofylin aplikace a dávkování chemie MeSH
- uvolňování léčiv MeSH
- voda MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin. METHODS: To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of D-glucose derivatives, both hydrophilic and amphiphilic. RESULTS: Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-D-glucopyranoside 5 as a promising enhancer. Furthermore, this amino sugar 5 increased epidermal concentration of a highly hydrophilic antiviral cidofovir by a factor of 7. The effect of compound 5 on skin electrical impedance suggested its direct interaction with the skin barrier. Infrared spectroscopy of isolated stratum corneum revealed no effect of enhancer 5 on the stratum corneum proteins but an overall decrease in the lipid chain order. The enhancer showed acceptable toxicity on HaCaT keratinocyte and 3T3 fibroblast cell lines. Finally, transepidermal water loss returned to baseline values after enhancer 5 had been removed from the skin. CONCLUSIONS: Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.
- MeSH
- antivirové látky aplikace a dávkování metabolismus MeSH
- aplikace kožní MeSH
- aplikace lokální MeSH
- buněčné linie MeSH
- chemie farmaceutická MeSH
- cytosin aplikace a dávkování analogy a deriváty metabolismus MeSH
- epidermis účinky léků metabolismus MeSH
- glukosidy chemická syntéza farmakologie MeSH
- hexosy farmakologie MeSH
- hydrofobní a hydrofilní interakce MeSH
- keratinocyty účinky léků metabolismus MeSH
- kožní absorpce MeSH
- kůže účinky léků metabolismus MeSH
- lidé MeSH
- lipidy fyziologie MeSH
- organofosfonáty aplikace a dávkování metabolismus MeSH
- permeabilita MeSH
- systémy cílené aplikace léků MeSH
- theofylin aplikace a dávkování metabolismus MeSH
- viabilita buněk MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Assembly of human immunodeficiency virus (HIV-1) represents an attractive target for antiretroviral therapy which is not exploited by currently available drugs. We established high-throughput screening for assembly inhibitors based on competition of small molecules for the binding of a known dodecapeptide assembly inhibitor to the C-terminal domain of HIV-1 CA (capsid). Screening of >70000 compounds from different libraries identified 2-arylquinazolines as low micromolecular inhibitors of HIV-1 capsid assembly. We prepared focused libraries of modified 2-arylquinazolines and tested their capacity to bind HIV-1 CA to compete with the known peptide inhibitor and to prevent the replication of HIV-1 in tissue culture. Some of the compounds showed potent binding to the C-terminal domain of CA and were found to block viral replication at low micromolar concentrations.
- MeSH
- chinazoliny chemická syntéza chemie farmakologie MeSH
- HIV-1 účinky léků metabolismus MeSH
- kapsida účinky léků metabolismus MeSH
- knihovny malých molekul MeSH
- látky proti HIV metabolismus farmakologie MeSH
- lidé MeSH
- molekulární modely MeSH
- rekombinantní proteiny biosyntéza MeSH
- replikace viru účinky léků MeSH
- reprodukovatelnost výsledků MeSH
- rychlé screeningové testy MeSH
- termodynamika MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The syntheses of the unprotected neutral closo-carboranyl-C-deoxyriboses, starting from anomeric mixture of 1-ethynyldeoxyriboses, and their corresponding open-cage nido-derivatives have been described. The structures of both the α- and β-anomers were confirmed by single-crystal X-ray diffraction. While limited water solubility of the neutral closo-anomers led to high cytotoxicity, their cesium salts (nido-species) exhibited higher water solubility leading to lower cytotoxicity. However, in vitro boron neutron capture therapy (BNCT) investigation using the murine squamous cell carcinoma (SCCVII) cell lines showed that there are no significant differences between the survival fractions of the two species.
- MeSH
- isomerie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nukleosidy chemická syntéza chemie farmakologie terapeutické užití MeSH
- rozpustnost MeSH
- sloučeniny boru chemie MeSH
- techniky syntetické chemie MeSH
- terapie metodou neutronového záchytu (bor-10) MeSH
- voda chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Compounds with polyfluorinated molecular fragments possess unique properties associated with the presence of a large number of fluorine atoms that affect lipophilicity and conformational rigidity of the parent molecule along with other effects. The aim of this review is to provide an overview of synthesized compounds possessing perfluoroalkylated or polyfluorinated chains that have been tested for bioactivity or as potential drug candidates for the treatment of various diseases. As far as the length of the perfluoroalkylated chain is concerned the focus is centered on the compound bearing perfluoroethyl or tetrafluoroethyl as well as longer chains. The perfluoroalkylated compounds discussed are classified according to their biological activity.
- MeSH
- alkylace MeSH
- fluorokarbony chemie farmakologie MeSH
- lidé MeSH
- objevování léků * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
A simple two-step method for the selective preparation of anomerically pure 1α- and 1β-(indol-2-yl)deoxyribose derivatives was developed. The synthesis was based on the Sonogashira reaction of 1α- and 1β-ethynyldeoxyribose and 2-haloanilines followed by a Pd-complex catalyzed cyclization to the corresponding indolyldeoxyribosides.
