National Repository of Grey Literature 15 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
Monitoring of enzymatic enantioselective acetylation of gem-difluorinated alcohols by capillary electrophoresis
Šolínová, Veronika ; Pomeisl, Karel ; Lamatová, Nikola ; Pohl, Radek ; Brabcová, Jana ; Krečmerová, Marcela ; Kašička, Václav
A new fast and highly efficient capillary electrophoretic (CE) method has been developed for chiral analysis of non-charged gem-difluorinated alcohol (3-(benzyloxy)-1,1-difluoro-propan-2-ol) using sulfobutylether-β-CD as chiral selector. The method was applied for monitoring of enzymatic (lipase mediated) enantioselective acetylation of the above alcohol and for determination of enantiomeric purity of both substrates and products of the enzymatic reaction.
The synthesis of stable O-acetyl-adenosine diphosphoribose analogs and inhibitors of sirtuins
Dvořáková, Marcela ; Vaněk, Tomáš (advisor) ; Jindřich, Jindřich (referee) ; Krečmerová, Marcela (referee)
Acetylated adenosine diphosphoribose (OAADPR) is a product of protein deacetylation catalysed by class III of histone deacetylases called sirtuins. Sirtuins deacetylate histones and other proteins by unique mechanism coupled with consumption of stoichiometric amount of NAD+ . Sirtuins and OAADPR are implicated in the regulation of gene transcription, signalling and metabolic pathways and lifespan extension, thus preventing the development of age-related diseases. Even though, sirtuins are well studied, the exact biological role of OAADPR remains mainly unknown. Its further exploration is restricted by OAADPR's proneness to enzymatic hydrolysis. Therefore, non-hydrolysable analogues of OAADPR are needed to establish its biological function. These analogues are also expected to be competitive inhibitors of sirtuins, which may reveal their potential as therapeutic agents. A series of OAADPR analogues in which the acetate moiety was replaced with alkylcarbonate functionality has been synthesized. The studies of alkylcarbonate migration on furanoside scaffold have established the stability of alkylcarbonate vs. acetate under various conditions. Generally, alkylcarbonates are more stable than acetate under acidic or neutral conditions whereas under basic conditions they seem to be less stable....
Tyrosine-based prodrugs of acyclic nucleoside phosphonates
Tichý, Tomáš ; Pomeisl, Karel ; Krečmerová, Marcela ; McKenna, Ch. E.
Prodrug approach based on masking of a phosphonate function by ester linkage to a tyrosine promoiety has been developed. Results demonstrate that tyrosine is a promoiety providing drug conjugates with good chemical stability, bioavailability and efficient activation to active drug species. Another properties like metabolic stability and antiviral activity can be tuned by modification of the carboxyl function of the promoiety. Phosphonate monoester prodrugs were prepared by PyBOP coupling of a protected tyrosine promoiety with suitably derivatized phosphonate function of the parent drug. Phosphonate diester prodrugs were prepared by "synthon" approach, emloying alkylation of purine nucleobase with pre-prepared PME synthons bearing two protected tyrosine promoieties.
New amphiphilic prodrugs of adefovir and cidofovir
Tichý, Tomáš ; Andrei, G. ; Dračínský, Martin ; Holý, Antonín ; Balzarini, J. ; Snoeck, R. ; Krečmerová, Marcela
New adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl(oxyethyl) chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The antiviral activity of the prodrugs was evaluated in vitro. A loss in the antiviral activities of the hydroxylated decyl(oxyethyl) esters and hexaethyleneglycol esters of PMEA against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anticytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir.
Nucleosides containing 8-aza-7,9-dedeazaxanthine
Mařák, David ; Otmar, Miroslav ; Dračínský, Martin ; Krečmerová, Marcela
8-aza-7,9-dideazaxanthine nucleosides were prepared from 5-nitrouracil employing a Barton-Zard reaction.
Cyclic and acyclic phosphonate tyrosine ester prodrugs of acyclic nucleoside phosphonates
Williams, M. ; Krylov, I. S. ; Zakharova, V. M. ; Serpi, M. ; Peterson, L. W. ; Krečmerová, Marcela ; Kashemirov, B. A. ; McKenna, Ch. E.
A series of P-O ester derivatives of HPMPA, HPMPC, PMEA a (R)-PMPDAP was synthesized as potential anti-malarial prodrugs.
New strategies in synthesis of acyclic nucleoside phosphonate prodrugs
Krečmerová, Marcela ; Tichý, Tomáš ; Blažek, Jiří ; Pomeisl, Karel
New syntheses of acyclic nucleoside phosphonate prodrugs including dioxolenone derivatives, functionalized alkoxyalkyl esters, utilization of hexafluorophosphate coupling agents and enzymatic glycosylations were described. Comparison of antiviral activities of diverse prodrugs was performed.
9-[2-hydroxy-3-(phosphonomethoxy)propyl] ("iso-HPMP")derivatives of purine bases and their side-chain modified analogues: synthesis and antimalarial activity
Krečmerová, Marcela ; Holý, Antonín ; Hocková, Dana ; Dračínský, Martin ; Keough, D. T. ; Guddat, L. W.
Hypoxanthine and guanine iso-HPMP derivatives substsituted in 2´-position were prepared and studied as potential inhibitors of a key enzyme of the malarial parasite Plasmodium falciparum HGXPRT.
Chemical synthesis of prodrugs derived from 5,6-dihydro-5-azacytosine and its nucleosides using vinyl esters
Janská, Lucie ; Blažek, Jiří ; Mařák, David ; Otmar, Miroslav ; Krečmerová, Marcela
New strategy for synthesis of amide prodrugs without protecting groups for 5,6-dihydro-5-azacytosine and its nucleosides was developed and introduced. Vinyl esters were used as acyl donor and the reactive amino group on the heterocycle functions as nucleophile.
Enzymatic synthesis of ester prodrugs of DHPA and related compounds by lipases
Blažek, Jiří ; Kaiser, M. M. ; Zarevúcka, Marie ; Králová, B. ; Krečmerová, Marcela
An enzymatic method was used for esterification of DHPA and related compounds with vinyl esters and catalyzed by different lipases in non-aqueous media (DMF). Esters of DHPA and other compounds could be synthesized and purified in satisfactory yields.

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