monosubstitution
Dotaz
Zobrazit nápovědu
Alkylation of cyclomaltohexaose (α-cyclodextrin, α-CD) with allyl or cinnamyl bromide, followed by peracetylation of remaining hydroxyl groups and separation of isomers, resulted in the set of peracetylated 2(I)-O-, 3(I)-O- and 6(I)-O-alkylated α-CDs in up to 27% yields. Ozonolysis or oxidative cleavage of peracetylated allyl or cinnamyl derivatives resulted in a complete set of peracetylated 2(I)-O-, 3(I)-O- and 6(I)-O-formylmethyl or carboxymethyl derivatives that are useful precursors for preparation of regioselectively monosubstituted derivatives of α-CD. Moreover, a quick method to recognize single 2(I)-O-, 3(I)-O- and 6(I)-O-monosubstituted peracetylated CDs from one another using only their (1)H NMR spectra has been proposed.
- MeSH
- acetylace MeSH
- aldehydy chemická syntéza MeSH
- alfa-cyklodextriny chemická syntéza chemie izolace a purifikace MeSH
- alkylace MeSH
- katalýza MeSH
- kyseliny karboxylové chemická syntéza MeSH
- magnetická rezonanční spektroskopie MeSH
- oxidace-redukce MeSH
- síran měďnatý chemie MeSH
- sloučeniny ruthenia chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The research of innovative antimicrobial agents represents a cutting edge topic. Hence, we synthesized and characterised novel salicylanilide N-monosubstituted carbamates. Twenty compounds were evaluated in vitro against eight bacterial strains and eight fungal species. The lowest minimum inhibitory concentrations (MICs) were found to be ⩽0.49 μM. Genus Staphylococcus, including methicillin-resistant Staphylococcus aureus, and fungus Trichophyton mentagrophytes showed uniformly the highest rate of susceptibility, whilst Gram-negative bacteria and most of the fungi were less susceptible. A wide range of carbamates provided comparable or superior in vitro antimicrobial activity in comparison to established drugs. Interestingly, extended-spectrum β-lactamase producing strain of Klebsiella pneumoniae was inhibited with MICs starting from 31.25 μM. With respect to Staphylococci, 2-[(4-bromophenyl)carbamoyl]-4-chlorophenyl phenylcarbamate exhibited the lowest MIC values (⩽0.98 μM). 2-[(4-Bromophenyl)carbamoyl]-4-chlorophenyl benzylcarbamate showed the widest spectrum of antifungal action. The results indicate that some salicylanilide carbamates can be considered to be promising candidates for future investigation.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- antifungální látky chemická syntéza chemie farmakologie MeSH
- gramnegativní bakterie účinky léků MeSH
- houby účinky léků MeSH
- karbamáty chemická syntéza chemie farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- salicylanilidy chemická syntéza chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The research of novel antimycobacterial drugs represents a cutting-edge topic. Thirty phenolic N-monosubstituted carbamates, derivatives of salicylanilides and 4-chlorophenol, were investigated against Mycobacterium tuberculosis H37Ra, H37Rv including multidrug- and extensively drug-resistant strains, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium aurum and Mycobacterium smegmatis as representatives of nontuberculous mycobacteria (NTM) and for their cytotoxic and cytostatic properties in HepG2 cells. Since salicylanilides are multi-targeting compounds, we determined also inhibition of mycobacterial isocitrate lyase, an enzyme involved in the maintenance of persistent tuberculous infection. The minimum inhibitory concentrations were from ≤0.5 μM for both drug-susceptible and resistant M. tuberculosis and from ≤0.79 μM for NTM with no cross-resistance to established drugs. The presence of halogenated salicylanilide scaffold results into an improved activity. We have verified that isocitrate lyase is not a key target, presented carbamates showed only moderate inhibitory activity (up to 18% at a concentration of 10 μM). Most of the compounds showed no cytotoxicity for HepG2 cells and some of them were without cytostatic activity. Cytotoxicity-based selectivity indexes of several carbamates for M. tuberculosis, including resistant strains, were higher than 125, thus favouring some derivatives as promising features for future development.
- MeSH
- antituberkulotika chemická syntéza chemie farmakologie MeSH
- buňky Hep G2 MeSH
- fenoly chemická syntéza chemie farmakologie MeSH
- isocitrátlyasa antagonisté a inhibitory metabolismus MeSH
- karbamáty chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- Mycobacterium tuberculosis účinky léků enzymologie MeSH
- salicylanilidy chemická syntéza chemie farmakologie MeSH
- tuberkulóza farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Based on the presence of carbamate moiety, twenty salicylanilide N-monosubstituted carbamates concomitantly with their parent salicylanilides and five newly prepared 4-chlorophenyl carbamates obtained from isocyanates were investigated using Ellman's method for their in vitro inhibitory activity against acetylcholinesterase (AChE) from electric eel and butyrylcholinesterase (BChE) from equine serum. The carbamates and salicylanilides exhibited mostly a moderate inhibition of both cholinesterase enzymes with IC50 values ranging from 5 to 235 µM. IC50 values for AChE were in a narrower concentration range when compared to BChE, but many of the compounds produced a balanced inhibition of both cholinesterases. The derivatives were comparable or superior to rivastigmine for AChE inhibition, but only a few of carbamates also for BChE. Several structure-activity relationships were identified, e.g., N-phenethylcarbamates produce clearly favourable BChE inhibition. The compounds also share convenient physicochemical properties for CNS penetration.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- butyrylcholinesterasa metabolismus MeSH
- chlorfenoly chemie farmakologie MeSH
- cholinesterasové inhibitory chemie farmakologie MeSH
- Electrophorus MeSH
- inhibiční koncentrace 50 MeSH
- karbamáty chemie farmakologie MeSH
- koně MeSH
- salicylanilidy chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
