Due to their structural variability and their commercial availability, cyclodextrins are the most frequently used chiral selectors in capillary electrophoresis. A variety of migration modes can be realized depending on the characteristics of the cyclodextrins and the analytes. The basic considerations regarding the development of a chiral CE method employing cyclodextrins as chiral selectors are briefly discussed. The presented examples illustrate the separation modes of an acidic and a basic analyte with native and charged cyclodextrin derivatives as a function of the pH of the background electrolyte and the concentration of the cyclodextrin.
- Klíčová slova
- Capillary electrophoresis, Chiral separation, Cyclodextrin, Enantiomer migration order, Enantioseparation,
- MeSH
- cyklodextriny chemie MeSH
- elektroforéza kapilární metody MeSH
- koncentrace vodíkových iontů MeSH
- ofloxacin chemie izolace a purifikace MeSH
- oxid křemičitý chemie MeSH
- stereoizomerie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cyklodextriny MeSH
- ofloxacin MeSH
- oxid křemičitý MeSH
In order to provide a more detailed view on the structure⁻antimycobacterial activity relationship (SAR) of phenylcarbamic acid derivatives containing two centers of protonation, 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium oxalates (1a⁻d)/dichlorides (1e⁻h) as well as 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(di-propylammonio)propyl]azepanium oxalates (1i⁻l)/dichlorides (1m⁻p; alkoxy = butoxy to heptyloxy) were physicochemically characterized by estimation of their surface tension (γ; Traube's stalagmometric method), electronic features (log ε; UV/Vis spectrophotometry) and lipophilic properties (log kw; isocratic RP-HPLC) as well. The experimental log kw dataset was studied together with computational logarithms of partition coefficients (log P) generated by various methods based mainly on atomic or combined atomic and fragmental principles. Similarities and differences between the experimental and in silico lipophilicity descriptors were analyzed by unscaled principal component analysis (PCA). The in vitro activity of compounds 1a⁻p was inspected against Mycobacterium tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794, respectively), M. tuberculosis H37Ra ATCC 25177, M. kansasii CNCTC My 235/80 (identical with ATCC 12478), the M. kansasii 6509/96 clinical isolate, M. kansasii DSM 44162, M. avium CNCTC My 330/80 (identical with ATCC 25291), M. smegmatis ATCC 700084 and M. marinum CAMP 5644, respectively. In vitro susceptibility of the mycobacteria to reference drugs isoniazid, ethambutol, ofloxacin or ciprofloxacin was tested as well. A very unique aspect of the research was that many compounds from the set 1a⁻p were highly efficient almost against all tested mycobacteria. The most promising derivatives showed MIC values varied from 1.9 μM to 8 μM, which were lower compared to those of used standards, especially if concerning ability to fight M. tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 or M. avium CNCTC My 330/80. Current in vitro biological assays and systematic SAR studies based on PCA approach as well as fitting procedures, which were supported by relevant statistical descriptors, proved that the compounds 1a⁻p represented a very promising molecular framework for development of 'non-traditional' but effective antimycobacterial agents.
- Klíčová slova
- Mycobacterium spp., dibasic phenylcarbamates, electronic properties, lipophilicity, surface tension,
- MeSH
- antituberkulotika chemická syntéza farmakologie MeSH
- azepiny chemická syntéza farmakologie MeSH
- ciprofloxacin chemie terapeutické užití MeSH
- ethambutol chemie terapeutické užití MeSH
- fenylkarbamáty chemická syntéza farmakologie MeSH
- isoniazid chemie terapeutické užití MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium avium účinky léků MeSH
- Mycobacterium kansasii účinky léků MeSH
- Mycobacterium smegmatis účinky léků MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- Mycobacterium účinky léků MeSH
- ofloxacin chemie terapeutické užití MeSH
- oxaláty chemie farmakologie MeSH
- počítačová simulace MeSH
- pyrrolidiny chemická syntéza farmakologie MeSH
- racionální návrh léčiv MeSH
- rozpustnost MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antituberkulotika MeSH
- azepiny MeSH
- ciprofloxacin MeSH
- ethambutol MeSH
- fenylkarbamáty MeSH
- isoniazid MeSH
- ofloxacin MeSH
- oxaláty MeSH
- pyrrolidiny MeSH
