In this report, fluorescent systems consisting of two Rhodamine B moieties were designed and synthesized employing the solid-phase synthetic approach. The compounds were tested for their chemosensing behavior upon the addition of various metal ions over UV-vis absorption and fluorescence spectra. Two probes, 1 and 3, exhibited the best affinity to Sn(IV) ions, resulting in strong fluorescence as well as absorbance enhancement with the low detection limits (2.78 and 2.56 μM, respectively). Compound 3 having two excitations as well as emission maxima was used for the construction of the light dimmer with the alarm for detection of too low pH. The system is operated by a change of pH and can be used as a molecular electronic device.
- Publikační typ
- časopisecké články MeSH
Racemic 2-(2-trifluoromethyl)-1H-benzo[d]imidazol-1-yl)benzoic acid (TBBA) was synthesized in three steps from 1-fluoro-2-nitrobenzene. Target (P)- and (M)-TBBA atropisomers were stable with a racemization barrier above 30 kcal/mol. As a chiral derivatizing agent, TBBA showed much higher differences in chemical shifts (ΔδPM) than the conventional Mosher's acid.
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIM: From betulinic acid (1a), we synthesized 30-oxobetulinic acid (2a) that is highly cytotoxic against many cancer cell lines; however, its generic toxicity is the main obstacle in further development as cytostatic. Methodology & results: From 2a, we prepared a new class of compounds - nonsymmetrical azines and tested their in vitro cytotoxicity. All new azines with a free 28-COOH group (4a-4e) were highly and selectively cytotoxic against the T-lymphoblastic leukemia cell line CCRF-CEM and exhibited dose-dependent inhibition of RNA and DNA synthesis and other cell-cycle alterations, including the M-phase block. CONCLUSION: The potential use of azines (4a-4e) in drug development focused on hematological cancers is significantly higher than that of previously studied acids 1a and 2a.
- Klíčová slova
- betulinic acid, cytotoxicity, hydrazone,
- MeSH
- buněčné linie MeSH
- fytogenní protinádorové látky chemická syntéza chemie farmakologie MeSH
- hydraziny chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- molekulární konformace MeSH
- proliferace buněk účinky léků MeSH
- screeningové testy protinádorových léčiv MeSH
- triterpeny chemická syntéza chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fytogenní protinádorové látky MeSH
- hydraziny MeSH
- triterpeny MeSH
Herein, we report the stereoselective synthesis of trisubstituted benzoxazino[4,3-b][1,2,5]thiadiazepinone 6,6-dioxides from polymer-supported Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH. After the solid-phase synthesis of N-alkylated-N-sulfonylated intermediates using various 2-nitrobenzenesulfonyl chlorides and bromoketones, the target compounds were obtained via trifluoroacetic acid (TFA)-mediated cleavage from the resin, followed by cyclization of the diazepinone scaffold. Except for the threonine-based intermediates, the inclusion of triethylsilane (TES) in the cleavage cocktail yielded a specific configuration of the newly formed C3 chiral center. The final cyclization resulted in minor or no inversion of the C12a stereocenter configuration.
- Klíčová slova
- benzoxazinothiadiazepinone, bromoketone, cysteine, morpholine, nitrobenzenesulfonyl chloride, serine, solid-phase synthesis, stereoselective synthesis, thiomorpholine, threonine, triethylsilane,
- MeSH
- alkylace MeSH
- cyklické S-oxidy chemická syntéza MeSH
- cyklizace MeSH
- knihovny malých molekul chemická syntéza MeSH
- polymery chemie MeSH
- stereoizomerie MeSH
- techniky syntézy na pevné fázi MeSH
- thiadiazoly chemická syntéza MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cyklické S-oxidy MeSH
- knihovny malých molekul MeSH
- polymery MeSH
- thiadiazoly MeSH
Herein we report the polymer-supported synthesis of 3,4-dihydro-2H-1,4-oxazine-3-carboxylic acid derivatives using immobilized Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH as the starting materials. After the solid-phase-synthesis of N-alkyl-N-sulfonyl/acyl intermediates, the target dihydrooxazines were obtained using trifluoroacetic acid-mediated cleavage from the resin. This approach was also studied for the preparation of dihydrothiazines from immobilized Fmoc-Cys(Trt)-OH. Inclusion of triethylsilane in the cleavage cocktail resulted in the stereoselective formation of the corresponding morpholine/thiomorpholine-3-carboxylic acids. Stereochemical studies revealed the specific configuration of the newly formed stereocenter and also the formation of stable N-acylmorpholine rotamers.
- Klíčová slova
- amino acid, bromoketone, morpholine, nitrobenzenesulfonyl chloride, oxazine, solid-phase synthesis, stereoselective synthesis, thiazine, thiomorpholine,
- MeSH
- fluoreny chemie MeSH
- kyseliny karboxylové chemická syntéza chemie MeSH
- morfoliny chemická syntéza chemie MeSH
- oxaziny chemická syntéza chemie MeSH
- polymery chemie MeSH
- stereoizomerie MeSH
- techniky syntézy na pevné fázi metody MeSH
- thiaziny chemická syntéza chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fluoreny MeSH
- kyseliny karboxylové MeSH
- morfoliny MeSH
- oxaziny MeSH
- polymery MeSH
- thiamorpholine MeSH Prohlížeč
- thiaziny MeSH
The proposed HPLC method using solely or nearly 100% aqueous mobile buffer as mobile phase offers fast determination of dissociation constant for compounds in relatively wide range of lipophilicity (log P from -2.26 to 2.26). The dissociation constant value for simpler chemical compounds can be determined via only 8 chromatographic runs. The number of needed chromatographic separations depends on the structural complexity of the tested compound. Moreover, the proposed method does not require a measurement of Yasuda-Shedlovsky extrapolation that includes several pKa determinations in solutions with different methanol content which speeds up considerably the procedure. The methodology is suitable for evaluation of large series of drug candidates, which can be present as complex mixtures and in small amounts.
- Klíčová slova
- Dissociation constant, HPLC, High-throughput measurement, Reversed phase,
- MeSH
- chromatografie s reverzní fází metody MeSH
- voda analýza chemie metabolismus MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- voda MeSH
Derivatives of 3-methyl-3,6-dihydro-2H-1,2-oxazine-6-carboxylic acid prepared by regioselective hetero Diels-Alder reaction of arylnitroso compounds with sorbic acid were used for solid-phase synthesis of a library of derivatives that included modification of carboxylic group, dihydroxylation of double bond and cleavage of N-O bond. Derivatives of 2,3,4-trihydroxyhexanoic acid obtained from 3,6-dihydro-2H-1,2-oxazines after double bond dihydroxylation and N-O cleavage were used for simple and stereoselective formation of chiral lactones derived from 3,4-dihydroxydihydrofuran-2(3H)-one. The final compounds obtained as a mixture of stereoisomers were analyzed with use of chiral HPLC and SFC. HPLC analyses were not successful for all derivatives or required lengthy chromatography. On the other hand SFC afforded much shorter analyses and was effective for all studied derivatives. The method of synthesis and analysis is thus suitable for future study of stereoselective synthesis of lactones and other derivatives from single oxazine derivatives and application of high-throughput synthesis on solid-support and combinatorial chemistry.
- MeSH
- cykloadiční reakce MeSH
- hmotnostní spektrometrie MeSH
- laktony chemická syntéza chemie MeSH
- magnetická rezonanční spektroskopie MeSH
- oxaziny chemická syntéza chemie MeSH
- stereoizomerie MeSH
- techniky syntézy na pevné fázi MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- laktony MeSH
- oxaziny MeSH
Synthesis of 2,3-dihydrobenzo[f][1,2,5]thiadiazepin-4(5H)-one 1,1-dioxides from polymer-supported α-amino acids is described herein. Different α-amino acids immobilized on Wang resin were sulfonylated with various 2-nitrobenzenesulfonyl chlorides. The resulting 2-nitrobenzenesulfonamides were alkylated with alcohols according to the Fukuyama-Mitsunobu procedure. After reduction of the nitro group and cleavage from the polymer support, the final intermediates were reacted with thionyl chloride, and target compounds of good crude purity and acceptable overall yields were obtained. The chiral HPLC studies revealed the impact of the cyclization step on the resulting stereochemistry. The developed strategy allows for simple production of desired compounds with the application of parallel/combinatorial solid-phase synthesis using commercially available building blocks.
- Klíčová slova
- 2-nitrobenzenesulfonyl chlorides, Fukuyama−Mitsunobu alkylation, solid-phase synthesis, thiadiazepin-4(5H)-one 1,1-dioxides,
- MeSH
- aminokyseliny chemie MeSH
- benzenové deriváty chemická syntéza MeSH
- cyklizace MeSH
- oxidy chemická syntéza MeSH
- techniky kombinatorické chemie MeSH
- techniky syntézy na pevné fázi metody MeSH
- thiazepiny chemická syntéza MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aminokyseliny MeSH
- benzenové deriváty MeSH
- oxidy MeSH
- thiazepiny MeSH
Quercetin and phenylpropanoids are well known chemoprotective compounds identified in many plants. This study was aimed at determining their effects on activation of Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element (Nrf2-ARE) signalling pathway and expression of its important downstream effector phase II detoxification enzyme glutathione-S-transferase P1 (GSTP1) in BJ foreskin fibroblasts and skin HaCaT keratinocytes. Cell lines and their corresponding Nrf2-ARE luciferase reporter cells were treated by ginger phenylpropanoids and quercetin for 10 h and the level of Nrf2 activity was subsequently determined. Both, ginger phenylpropanoids and quercetin, significantly increased the level of Nrf2 activity. Subsequent western blot analyses of proteins showed the increased expression level of glutathione-S-transferase P1 (GSTP1) in BJ cells but not in HaCaT cells. Such phenomenon of unresponsive downstream target expression in HaCaT cells was consistent with previous studies showing a constitutive expression of their GSTP1. Thus, while both ginger phenylpropanoids and quercetin have the property of increasing the level of Nrf2 both in HaCaT and in BJ cells, their effects on its downstream signalling were mediated only in BJ cells.
- MeSH
- antioxidancia aplikace a dávkování chemie MeSH
- buněčné linie MeSH
- faktor 2 související s NF-E2 biosyntéza genetika MeSH
- fibroblasty účinky léků metabolismus MeSH
- glutathion-S-transferasa fí biosyntéza genetika MeSH
- glutathiontransferasa MeSH
- keratinocyty účinky léků metabolismus MeSH
- lidé MeSH
- quercetin aplikace a dávkování MeSH
- regulace genové exprese účinky léků MeSH
- signální transdukce účinky léků MeSH
- zázvor lékařský chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia MeSH
- faktor 2 související s NF-E2 MeSH
- glutathion-S-transferasa fí MeSH
- glutathiontransferasa MeSH
- leukotriene-C4 synthase MeSH Prohlížeč
- quercetin MeSH
Resin-bound intermediates prepared from polymer-supported amino acid esters, 2-nitrobenezenesulfonyl chlorides, and alcohols were used to synthesize 3-alkyl-3-(alkylamino) indolin-2-ones. The key step of the reaction sequence was the formation of a quaternary carbon via the base-mediated C-arylation of 2-nitrobenzenesulfonamides. The cleavage of the acyclic precursors from the resin and subsequent reduction of the nitro group by Zn in acetic acid triggered the spontaneous cyclization of the arylated compounds to indolinones. The synthesis was carried out using simple commercially available building blocks under mild conditions and provided the 3,3-disubstituted indolinone derivatives with good overall yields however, the arylation reaction resulted in the epimerization of the quaternary carbon.
- Klíčová slova
- C−C bond formation, arylation, heterocycle, nitrobenzenesulfonamides, oxindole, quaternary carbon, solid-phase synthesis,
- MeSH
- indoly chemická syntéza chemie MeSH
- molekulární struktura MeSH
- sulfonamidy chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- indolin-2-one MeSH Prohlížeč
- indoly MeSH
- sulfonamidy MeSH
