Bacteria have developed different intra- and inter-specific communication mechanisms that involve the production, release, and detection of signaling molecules, because these molecules serve as the autoinducers involved in "quorum sensing" systems. Other communication mechanisms employ volatile signaling molecules that regulate different bacterial processes. The Arthrobacter agilis strain UMCV2 is a plant growth promoting actinobacterium, which induces plant growth and inhibits phytopathogenic fungi by emitting the dimethylhexadecylamine (DMHDA). However, little is known about the effect of this volatile compound on A. agilis UMCV2 itself, as well as on other bacteria. By exposing A. agilis UMCV2 and bacteria of the genus Bacillus and Pseudomonas to different concentrations of DMHDA, this study showed the dose-dependent effects of DMHDA on A. agilis UMCV2 growth, cellular viability, swarming motility, and expression of marker genes of the flagellar apparatus of bacteria. DMHDA was found to also modulate swarming motility of Bacillus sp. ZAP018 and P. fluorescens UM270, but not that of P. aeruginosa PA01. These data indicate that DMHDA is involved in both intra- and inter-specific bacterial interaction.

• MeSH
• Arthrobacter účinky léků   růst a vývoj   MeSH
• Bacillus účinky léků   růst a vývoj   MeSH
• methylaminy farmakologie   MeSH
• mikrobiální interakce účinky léků   MeSH
• pohyb účinky léků   MeSH
• Pseudomonas účinky léků   růst a vývoj   MeSH
• quorum sensing účinky léků   MeSH
• těkavé organické sloučeniny farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hexadecyldimethylamine MeSH Prohlížeč
• methylaminy MeSH
• těkavé organické sloučeniny MeSH

Oligonucleotides modified by clinically ineffective trans-diamminedichloridoplatinum(II) (transplatin) have been shown to be effective modulators of gene expression. This is so because in some nucleotide sequences the 1,3-GNG intrastrand adducts formed by transplatin in double-helical DNA readily rearrange into interstrand cross-links so that they can cross-link the oligonucleotides to their targets. On the other hand, in a number of other sequences these intrastrand adducts are relatively stable, which represents the major difficulty in the clinical use of the antisense transplatin-modified oligonucleotides. Therefore, we examined in this study, the stability of 1,3-GNG intrastrand adducts in double-helical DNA formed by a new antitumor derivative of transplatin, trans-[Pt(CH3NH2)2Cl2], in the sequence contexts in which transplatin formed relatively stable intrastrand cross-links which did not readily rearranged into interstrand cross-links. We have found that 1,3-GNG intrastrand adducts in double-helical DNA formed by trans-[Pt(CH3NH2)2Cl2] even in such sequences readily rearrange into interstrand cross-links. This work also suggests that an enhanced frequency of intrastrand cross-links yielded by trans-[Pt(CH3NH2)2Cl2] is a consequence of the fact that these DNA lesions considerably distort double-helical DNA in far more sequence contexts than parent transplatin. Our results suggest that trans-[Pt(CH3NH2)2Cl2]-modified oligonucleotides represent promising candidates for new agents in antisense or antigene approach.

• MeSH
• adukty DNA chemie   MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• cisplatina chemie   farmakologie   MeSH
• DNA chemie   MeSH
• lidé MeSH
• ligandy MeSH
• methylaminy chemie   farmakologie   MeSH
• oligonukleotidy chemie   farmakologie   MeSH
• reagencia zkříženě vázaná chemie   farmakologie   MeSH
• sekvence nukleotidů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adukty DNA MeSH
• antitumorózní látky MeSH
• cisplatina MeSH
• DNA MeSH
• ligandy MeSH
• methylamine MeSH Prohlížeč
• methylaminy MeSH
• oligonukleotidy MeSH
• reagencia zkříženě vázaná MeSH
• transplatin MeSH Prohlížeč

The inhibition of overactive CDKs during cancer remains an important strategy in cancer drug development. We synthesized and screened a novel series of 2-substituted-6-biarylmethylamino-9-cyclopentylpurine derivatives for improved CDK inhibitory activity and antiproliferative effects. One of the most potent compounds, 6b, exhibited strong cytotoxicity in the human melanoma cell line G361 that correlated with robust CDK1 and CDK2 inhibition and caspase activation. In silico modeling of 6b in the active site of CDK2 revealed a high interaction energy, which we believe is due to the 6-heterobiarylmethylamino substitution of the purine moiety.

• MeSH
• adenin analogy a deriváty   chemická syntéza   chemie   farmakologie   MeSH
• antitumorózní látky chemická syntéza   chemie   farmakologie   MeSH
• apoptóza MeSH
• cyklin-dependentní kinasa 2 antagonisté a inhibitory   MeSH
• cyklin-dependentní kinasy antagonisté a inhibitory   MeSH
• cyklopentany chemická syntéza   chemie   farmakologie   MeSH
• fosforylace MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• methylaminy chemická syntéza   chemie   farmakologie   MeSH
• molekulární modely MeSH
• nádorové buněčné linie MeSH
• počítačová simulace MeSH
• proteinkinasa CDC2 antagonisté a inhibitory   MeSH
• puriny chemická syntéza   chemie   farmakologie   MeSH
• retinoblastomový protein metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenin MeSH
• antitumorózní látky MeSH
• cyklin-dependentní kinasa 2 MeSH
• cyklin-dependentní kinasy MeSH
• cyklopentany MeSH
• methylaminy MeSH
• N2-(4-aminocyclohexyl)-9-cyclopentyl-N6-(6-(2-hydroxyphenyl)pyridin-3-ylmethyl)-9H-purine-2,6-diamine MeSH Prohlížeč
• proteinkinasa CDC2 MeSH
• puriny MeSH
• retinoblastomový protein MeSH

The universal protease inhibitors of the alpha(2)-macroglobulin (alpha(2)M) family are evolutionarily conserved constituents of innate immunity, presumably because they guard organisms against undesired proteolytic attacks of a different origin. Here, we determined the primary structure of alpha(2)-macroglobulin from the hard tick Ixodes ricinus (IrAM) by sequencing of overlapping PCR products. Predicted disulfide and glycosylation patterns, post-translational cleavage and alternative splicing within its 'bait region' demonstrate that IrAM is closely related to the alpha(2)-macroglobulin from the soft tick Ornithodoros moubata. The IrAM message is expressed in all tick developmental stages and tissues, except for the gut, and the protein was detected to be mainly present in the hemolymph. Silencing of IrAM by dsRNA interference markedly reduced the phagocytosis of a potential pathogen, Chryseobacterium indologenes, by tick hemocytes both in vitro and in vivo. In contrast, phagocytosis of the Lyme disease spirochete Borrelia burgdorferi or a commensal bacteria Staphylococcus xylosus was not affected by the IrAM knock-down. Similar results were obtained upon deactivation of all thioester proteins in tick hemolymph by methylamine. We have further demonstrated that phagocytosis of C. indologenes is dependent on an active metalloprotease secreted by the bacteria. These data indicate that interaction of tick alpha(2)-macroglobulin with a protease of an invading pathogen is linked with cellular immune response.

• MeSH
• alfa-makroglobuliny chemie   genetika   imunologie   farmakologie   MeSH
• Chryseobacterium imunologie   MeSH
• fagocytóza imunologie   MeSH
• fenantroliny farmakologie   MeSH
• hemocyty účinky léků   imunologie   mikrobiologie   MeSH
• hemolymfa imunologie   MeSH
• klíště genetika   imunologie   mikrobiologie   MeSH
• metaloproteasy účinky léků   metabolismus   MeSH
• methylaminy farmakologie   MeSH
• molekulární sekvence - údaje MeSH
• RNA interference MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,10-phenanthroline MeSH Prohlížeč
• alfa-makroglobuliny MeSH
• fenantroliny MeSH
• metaloproteasy MeSH
• methylamine MeSH Prohlížeč
• methylaminy MeSH

PURPOSE: Series of N,N-dimethylamino acid esters was synthesized to study their transdermal permeation-enhancing potency, biodegradability and reversibility of action. Effects of chirality, linking chain length and polyfluorination were investigated. MATERIALS AND METHODS: In vitro activities were evaluated using porcine skin and four model drugs-theophylline, hydrocortisone, adefovir and indomethacin. Biodegradability was determined using porcine esterase, reversibility was measured using electrical resistance. RESULTS: No differences in activity were found between (R), (S) and racemic dodecyl 2-(dimethylamino)propanoate (DDAIP). Substitution of hydrocarbon tail by fluorocarbon one resulted in loss of activity. Replacement of branched linking chain between nitrogen and ester of DDAIP by linear one markedly improved penetration-enhancing activity with optimum in 4-6C acid derivatives. Dodecyl 6-(dimethylamino)hexanoate (DDAK) was more potent than clinically used skin absorption enhancer DDAIP for theophylline (enhancement ratio of DDAK and DDAIP was 17.3 and 5.9, respectively), hydrocortisone (43.2 and 11.5) and adefovir (13.6 and 2.8), while DDAIP was better enhancer for indomethacin (8.7 and 22.8). DDAK was rapidly metabolized by porcine esterase, and displayed low acute toxicity. Electrical resistance of DDAK-treated skin barrier promptly recovered to control values. CONCLUSION: DDAK, highly effective, broad-spectrum, biodegradable and reversible transdermal permeation enhancer, is promising candidate for future research.

• MeSH
• adenin analogy a deriváty   metabolismus   MeSH
• alanin aplikace a dávkování   analogy a deriváty   chemická syntéza   farmakologie   MeSH
• aplikace kožní MeSH
• časové faktory MeSH
• chemie farmaceutická MeSH
• dimethylaminy MeSH
• dodekanol MeSH
• elektrická impedance MeSH
• esterasy metabolismus   MeSH
• halogenace MeSH
• hydrokortison metabolismus   MeSH
• hydrolýza MeSH
• indomethacin metabolismus   MeSH
• isomerie MeSH
• kapronáty aplikace a dávkování   chemická syntéza   farmakologie   MeSH
• kožní absorpce účinky léků   MeSH
• kůže účinky léků   metabolismus   MeSH
• methylaminy aplikace a dávkování   chemická syntéza   farmakologie   MeSH
• molekulární struktura MeSH
• nosiče léků MeSH
• organofosfonáty metabolismus   MeSH
• prasata MeSH
• příprava léků MeSH
• stabilita léku MeSH
• theofylin metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• adefovir MeSH Prohlížeč
• adenin MeSH
• alanin MeSH
• dimethylaminy MeSH
• dodecyl 2-(N,N-dimethylamino)propionate MeSH Prohlížeč
• dodecyl 6-(dimethylamino)hexanoate MeSH Prohlížeč
• dodekanol MeSH
• esterasy MeSH
• hydrokortison MeSH
• indomethacin MeSH
• kapronáty MeSH
• methylaminy MeSH
• nosiče léků MeSH
• organofosfonáty MeSH
• theofylin MeSH

Adefovir (9-(2-phosphonomethoxyethyl)adenine) is an acyclic nucleoside phosphonate currently used for the treatment of hepatitis B. The aim of this study was to evaluate the effect of permeation enhancer DDAK (6-dimethylaminohexanoic acid dodecyl ester) on the transdermal and topical delivery of adefovir. In porcine skin, DDAK enhanced adefovir flux 42 times with maximum at pH 5.8 suggesting ion pair formation. DDAK increased thermodynamic activity and stratum corneum/vehicle distribution coefficient of adefovir, as well as it directly decreased the skin barrier resistance. Maximal flux was observed already at 2% adefovir+1% DDAK. The results were confirmed in freshly excised human skin where DDAK enhanced adefovir flux 179 times to 8.9 microg/cm(2)/h. This rate of percutaneous absorption would allow for reaching effective plasma concentrations. After the topical application, adefovir concentrated in the stratum corneum with low penetration into the deeper skin layers from either aqueous or isopropyl myristate vehicle without the enhancer. With 1% DDAK, adefovir concentrations in the viable epidermis and dermis were 33-61 times higher. These results offer an attractive alternative to established routes of administration of adefovir and other acyclic nucleoside phosphonates.

• MeSH
• adenin aplikace a dávkování   analogy a deriváty   chemie   metabolismus   MeSH
• antivirové látky aplikace a dávkování   chemie   metabolismus   MeSH
• aplikace kožní MeSH
• chemie farmaceutická MeSH
• difuzní komory kultivační MeSH
• dimethylaminy MeSH
• dodekanol MeSH
• druhová specificita MeSH
• farmaceutická vehikula chemie   MeSH
• kapronáty chemie   farmakologie   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• kožní absorpce účinky léků   MeSH
• kůže účinky léků   metabolismus   MeSH
• lidé MeSH
• methylaminy chemie   farmakologie   MeSH
• organofosfonáty aplikace a dávkování   chemie   metabolismus   MeSH
• permeabilita MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adefovir MeSH Prohlížeč
• adenin MeSH
• antivirové látky MeSH
• dimethylaminy MeSH
• dodecyl 6-(dimethylamino)hexanoate MeSH Prohlížeč
• dodekanol MeSH
• farmaceutická vehikula MeSH
• kapronáty MeSH
• methylaminy MeSH
• organofosfonáty MeSH

The antimicrobials (1-methyldodecyl)dimethylamine oxide and (1-methyldodecyl)trimethylammonium bromide affect the cytoplasmic membrane of E. coli. The interaction results in release of intracellular material (K+, 260nm-absorbing material), an effect on dehydrogenase enzyme activity and inhibition of respiration. The final effect of both substances is the same; they differ only in their dynamics. The effect of the membrane was correlated with parameters characterizing these surfactants i.e. critical micelle concentration (c.m.c.) minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) over the concentration range of 10(-4) to 10(-1) mmol/dm3 of active substance. The three stage mode of action model can be summarized as follows: 1-polar (coulombic) interactions, 2-polar and hydrophobic interactions, 3-hydrophobic interactions (extraction and solubilization). The polar and hydrophobic interactions (1st and 2nd stage) are discussed also in relation to model membranes.

• MeSH
• buněčná membrána účinky léků   MeSH
• chemické jevy MeSH
• chemie fyzikální MeSH
• Escherichia coli účinky léků   ultrastruktura   MeSH
• kultivační média MeSH
• kvartérní amoniové sloučeniny chemická syntéza   farmakologie   MeSH
• methylaminy chemická syntéza   farmakologie   MeSH
• micely MeSH
• mikrobiální testy citlivosti MeSH
• nefelometrie a turbidimetrie MeSH
• oxidoreduktasy metabolismus   MeSH
• permeabilita buněčné membrány účinky léků   MeSH
• povrchové napětí MeSH
• spektrofotometrie infračervená MeSH
• spotřeba kyslíku účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kultivační média MeSH
• kvartérní amoniové sloučeniny MeSH
• methylaminy MeSH
• micely MeSH
• oxidoreduktasy MeSH
• tetramethylammonium MeSH Prohlížeč
• trimethyloxamine MeSH Prohlížeč

• MeSH
• adhezivita trombocytů účinky léků   MeSH
• aminokyseliny aplikace a dávkování   farmakologie   MeSH
• analýza rozptylu MeSH
• aprotinin aplikace a dávkování   farmakologie   MeSH
• benzensulfonáty farmakologie   MeSH
• časové faktory MeSH
• hemostatika farmakologie   MeSH
• hydrochinony farmakologie   MeSH
• injekce intravenózní MeSH
• kyseliny cyklohexankarboxylové farmakologie   MeSH
• kyseliny sulfonové aplikace a dávkování   farmakologie   MeSH
• lidé MeSH
• methylaminy farmakologie   MeSH
• metody MeSH
• trombocyty účinky léků   MeSH
• vyšetření krevní srážlivosti * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• aprotinin MeSH
• benzensulfonáty MeSH
• hemostatika MeSH
• hydrochinony MeSH
• kyseliny cyklohexankarboxylové MeSH
• kyseliny sulfonové MeSH
• methylaminy MeSH