A series of 2-aryl-2-(pyridin-2-yl)acetamides were synthesized and screened for their anticonvulsant activity in animal models of epilepsy. The compounds were broadly active in the 'classical' maximal electroshock seizure (MES) and subcutaneous Metrazol (scMET) tests as well as in the 6 Hz and kindling models of pharmacoresistant seizures. Furthermore, the compounds showed good therapeutic indices between anticonvulsant activity and motor impairment. Structure-activity relationship (SAR) trends clearly showed the highest activity resides in unsubstituted phenyl derivatives or compounds having ortho- and meta- substituents on the phenyl ring. The 2-aryl-2-(pyridin-2-yl)acetamides were derived by redesign of the cardiotoxic sodium channel blocker Disopyramide (DISO). Our results show that the compounds preserve the capability of the parent compound to inhibit voltage gated sodium currents in patch-clamp experiments; however, in contrast to DISO, a representative compound from the series 1 displays high levels of cardiac safety in a panel of in vitro and in vivo experiments.
- MeSH
- acetamidy aplikace a dávkování chemie terapeutické užití MeSH
- antikonvulziva aplikace a dávkování chemie terapeutické užití MeSH
- disopyramid aplikace a dávkování chemie terapeutické užití MeSH
- elektrický šok MeSH
- injekce intraperitoneální MeSH
- injekce subkutánní MeSH
- krysa rodu rattus MeSH
- molekulární struktura MeSH
- myši MeSH
- pentylentetrazol aplikace a dávkování MeSH
- potkani Wistar MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- záchvaty chemicky indukované farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Increasing production of energy crops in Europe, mainly maize and rapeseed, has altered patterns of pesticide use in recent decades. The long-term effects of S-metolachlor (S-M) and of its metabolite metolachlor OA (M-OA) at the environmentally relevant concentration of 4.2 μg L-1 and at 42 μg L-1 (ten-fold concentration) on marbled crayfish (Procambarus virginalis) were evaluated in a 28-day exposure and after a subsequent 28-day recovery period. Indicators assessed were behaviour; biochemical haemolymph profile; oxidative and antioxidant parameters of gill, hepatopancreas, and muscle; and histology of hepatopancreas and gill. Results showed biochemical haemolymph profile (lactate, alanine aminotransferase, aspartate aminotransferase, inorganic phosphate), lipid peroxidation in hepatopancreas, and antioxidant parameters (catalase, reduced glutathione, glutathione S-transferase) of hepatopancreas and gill of crayfish exposed to S-M and M-OA to significantly differ from controls (P < 0.01). Antioxidant biomarker levels remained different from controls after a 28-day recovery period. Differences in behaviour including speed of movement and velocity, and histopathological damage to gill and hepatopancreas were associated with S-M and M-OA exposure and persisted after 28 days in S-M- and M-OA-free water. Results suggest harmful effects of low concentrations of S-M and its metabolite M-OA on non-target organisms and provide information for assessing their effects at environmentally relevant concentrations.
- MeSH
- acetamidy chemie metabolismus farmakologie MeSH
- antioxidancia metabolismus MeSH
- chování zvířat účinky léků MeSH
- hemolymfa metabolismus MeSH
- hepatopankreas metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- severní raci účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Scadoxus puniceus (Amaryllidaceae), a medicinal plant of high value in South Africa, is used as a component of a traditional herbal tonic prescribed to treat several ailments. Ultra-high performance liquid chromatography-tandem mass spectrometry quantified the phenolic compounds in different organs of S. puniceus. Gravity column chromatography was used to separate fractions and active compounds. The structure of these compounds was determined using 1D and 2D nuclear magnetic resonance and mass spectroscopic techniques. A microplate technique was used to determine the acetylcholinesterase inhibitory activity of the pure compounds. Metabolite profiling revealed a greater profusion of hydroxycinnamic acids (69.5%), as opposed to hydroxybenzoic acids (30.5%). Chlorogenic acid was the most abundant (49.6% of hydroxycinnamic acids) compound. In addition to chlorogenic acid, the study is the first to report the presence of sinapic, gallic, and m-hydroxybenzoic acids in the Amaryllidaceae. Chromatographic separation of S. puniceus led to the isolation of haemanthamine (1), haemanthidine (2), and a rare chlorinated amide, metolachlor (3), the natural occurrence of which is described for the first time. Haemanthamine, haemanthidine, and metolachlor displayed strong acetylcholinesterase inhibitory activity (IC50 ; 23.1, 23.7, and 11.5 μM, respectively). These results substantiate the frequent use of S. puniceus as a medicinal plant and hold much promise for further pharmaceutical development.
- MeSH
- acetamidy chemie izolace a purifikace metabolismus farmakologie MeSH
- alkaloidy amarylkovitých chemie izolace a purifikace metabolismus farmakologie MeSH
- Amaryllidaceae chemie metabolismus MeSH
- cholinesterasové inhibitory chemie izolace a purifikace farmakologie MeSH
- fenantridiny chemie izolace a purifikace metabolismus farmakologie MeSH
- kyseliny kumarové chemie izolace a purifikace metabolismus farmakologie MeSH
- léčivé rostliny chemie MeSH
- rostlinné extrakty chemie izolace a purifikace metabolismus farmakologie MeSH
- tandemová hmotnostní spektrometrie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Jihoafrická republika MeSH
Nucleotides, 2'-deoxyribonucleoside triphosphates (dNTPs), and DNA probes bearing reactive chloroacetamido group linked to nucleobase (cytosine or 7-deazadaenine) through a propargyl tether were prepared and tested in cross-linking with cysteine- or histidine-containing peptides and proteins. The chloroacetamide-modifed dNTPs proved to be good substrates for DNA polymerases in the enzymatic synthesis of modified DNA probes. Modified nucleotides and DNA reacted efficiently with cysteine and cysteine-containing peptides, whereas the reaction with histidine was sluggish and low yielding. The modified DNA efficiently cross-linked with p53 protein through alkylation of cysteine and showed potential for cross-linking with histidine (in C277H mutant of p53).
Small neutral organic compounds have traditionally the role of EOF markers in electrophoresis, as they are expected to have zero electrophoretic mobility in external electric fields. The BGE contains, however, ions that have unequal affinities to the neutral molecules, which in turn results in their mobilization. In this study we focused on two EOF markers-thiourea and DMSO, as well as on N-methyl acetamide (NMA) as a model of the peptide bond. By means of CE and all atom molecular dynamics simulations we explored mobilization of these neutral compounds in large set of Hofmeister salts. Employing a statistical mechanics approach, we were able to reproduce by simulations the experimental electrophoretic mobility coefficients. We also established the role of the chemical composition of marker and the BGE on the measured electrophoretic mobility coefficient. For NMA, we interpreted the results in terms of the relative affinities of cations versus anions to the peptide bond.
- MeSH
- acetamidy chemie MeSH
- cesium chemie MeSH
- dimethylsulfoxid chemie MeSH
- elektroforéza kapilární metody MeSH
- elektroosmóza MeSH
- lithium chemie MeSH
- osmolární koncentrace MeSH
- roztoky MeSH
- simulace molekulární dynamiky MeSH
- soli MeSH
- thiomočovina chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- 13-C-methacetin, infračervená spektroskopie, transmitance, absorbance, kumulovaná dávka,
- MeSH
- acetamidy * diagnostické užití chemie MeSH
- analýza rozptylu MeSH
- dechové testy * metody přístrojové vybavení MeSH
- dospělí MeSH
- jaterní cirhóza * MeSH
- jaterní testy * MeSH
- játra patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- spektrofotometrie infračervená metody přístrojové vybavení MeSH
- srdeční selhání MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
The preemergence chloroacetamide herbicide metazachlor was encapsulated in biodegradable low molecular weight poly(lactic acid) micro- and submicroparticles, and its release to the water environment was investigated. Three series of particles, S, M, and L, varying in their size (from 0.6 to 8 μm) and with various initial amounts of the active agent (5%, 10%, 20%, 30% w/w) were prepared by the oil-in-water solvent evaporation technique with gelatin as biodegradable surfactant. The encapsulation efficiencies reached were about 60% and appeared to be lower for smaller particles. Generally, it was found that the rate of herbicide release decreased with increasing size of particles. After 30 days the portions of the herbicide released for its highest loading (30% w/w) were 92%, 56%, and 34% for about 0.6, 0.8, and 8 μm particles, respectively. The release rates were also lower for lower herbicide loadings. Metazachlor release from larger particles tended to be a diffusion-controlled process, while for smaller particles the kinetics was strongly influenced by an initial burst release.
- MeSH
- acetamidy chemie MeSH
- herbicidy chemie MeSH
- kinetika MeSH
- kyselina mléčná chemie MeSH
- léky s prodlouženým účinkem chemie MeSH
- molekulová hmotnost MeSH
- polymery chemie MeSH
- příprava léků metody MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
In this research, the adsorption of two herbicides, alachlor (ALA) and terbuthylazine (TBA), on granular activated carbon (GAC) in the presence of well-characterized peptide fraction of cellular organic matter (COM) produced by cyanobacterium Microcystis aeruginosa was studied. Two commercially available GACs were characterized using nitrogen gas adsorption and surface charge titrations. The COM peptides of molecular weight (MW) < 10 kDa were isolated and characterized using MW fractionation technique and high-performance size exclusion chromatography (HPSEC). The effect of surface charge on the adsorption of COM peptides was studied by means of equilibrium adsorption experiments at pH 5 and pH 8.5. Electrostatic interactions and hydrogen bonding proved to be important mechanisms of COM peptides adsorption. The adsorption of ALA and TBA on granular activated carbon preloaded with COM peptides was influenced by solution pH. The reduction in adsorption was significantly greater at pH 5 compared to pH 8.5, which corresponded to the increased adsorption of COM peptides at pH 5. The majority of the competition between COM peptides and both herbicides was attributed to low molecular weight COM peptides with MW of 700, 900, 1300 and 1700 Da.
- MeSH
- acetamidy analýza chemie MeSH
- adsorpce MeSH
- chemické látky znečišťující vodu analýza chemie MeSH
- dřevěné a živočišné uhlí chemie MeSH
- herbicidy analýza chemie MeSH
- kinetika MeSH
- Microcystis chemie MeSH
- odpad tekutý - odstraňování metody MeSH
- peptidy chemie MeSH
- povrchové vlastnosti MeSH
- triaziny analýza chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The condensation of substituted pyrazine-2-carboxylic acid chlorides with ring-substituted anilines yielded five substituted pyrazine-2-carboxylic acid amides. Thesynthesis, and analytical, lipophilicity and biological data of the newly synthesizedcompounds are presented in this paper. The photosynthesis inhibition, antialgal activityand the effect of a series of pyrazine derivatives as abiotic elicitors on the accumulation offlavonoids in a callus culture of Ononis arvensis (L.) were investigated. The most activeinhibitor of the oxygen evolution rate in spinach chloroplasts was 6-chloro-pyrazine-2-carboxylic acid (3-iodo-4-methylphenyl)-amide (2, IC(50) = 51.0 micromol.L(-1)). The highestreduction of chlorophyll content in Chlorella vulgaris was found for 5-tert-butyl-N-(4-chloro-3-methylphenyl)-pyrazine-2-carboxamide (3, IC(50) = 44.0 micromol.L(-1)). The maximalflavonoid production (about 900%) was reached after a twelve-hour elicitation processwith 6-chloropyrazine-2-carboxylic acid (3-iodo-4-methylphenyl)-amide (2).
