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1.
Lilliam Casillas-Martinez Millie L. Gonzalez Zamara Fuentes-Figueroa Cyd M. Castro Deborah Nieves-Mendez Carmen Hernandez 《Geomicrobiology journal》2013,30(6):269-281
Seasonal variations in precipitation changed the community composition and microbial activity in a hypersaline, tropical microbial mat, in Cabo Rojo, PR. Using a combination of dissection, light, and transmission electron microscopy, terminal restriction fragment length polymorphism (T-RFLP), in situ microelectrode studies, and 35 S isotope incubations, we documented the major differences between wet and dry seasons. During the wet season (precipitation 177 mm), cyanobacterial (green layer) and anoxyphototrophic (pink layer) communities, as well as the black FeS layer were well-developed, and T-RFLP patterns indicated a diverse community. The rate of oxygenic photosynthesis was 49 μ M min ? 1 . Aerobic respiration was 29 μ M min ? 1 , and sulfate reduction was 264 nmol cm ? 3 h ? 1 . During the dry season (precipitation 51 mm), cyanobacteria and anoxyphototrophs were less diverse and abundant, and T-RFLP patterns were less complex. The O 2 production rate was reduced to 9 μ M min ? 1 , as was O 2 consumption (7 μ M min ? 1 ) and sulfate reduction (26 nmol cm ? 3 h ? 1 ). Aragonite, calcite, halite, and quartz were the predominant minerals. Seasonal differences were found in the green and pink layers for both halite and quartz. Gypsum was not observed, likely due to a sample handling artifact. The fluctuations in community composition and metabolic activity, principally reflected in fluctuations in binding and trapping potential of the uppermost mat community, might be responsible for the observed differences in mineralogy. 相似文献
2.
Microbial growth inhibition and resistance to biological deterioration of concrete specimens coated with silver-loaded zeolite was evaluated by measuring the time course of bacterial growth, biological sulfur oxidation, and sulfate production using Acidithiobacillus thiooxidans as a corrosive agent. Live bacterial cells declined from an initial inoculum concentration of 1.1 × 104 cell ml-1 to zero in 10 days, during which only 0.5–1% of the initial sulfur concentration of 10 g l-1 was biologically oxidized, corresponding to sulfate production rates of 35–42 mg SO 4 2 ? g ? 1 S ? 1 . Leaching coefficients of calcium and silicon in the specimens coated with silver-loaded zeolite of 1.6 × 10 ? 4 to 4.6 × 10 ? 2 cm 2 d ? 1 respectively, were only 0.8% and 1% of the uncoated specimens. 相似文献
3.
AbstractZofenopril as an ACE inhibitor expired recently was found to have a favourable safety profile in comparison with other ACE inhibitors in treating high blood pressure, congestive heart failure, and acute myocardial infarction. It can be synthesised from the key building blocks of (S)-3-benzoylthio-2-methylpropanoic acid and (4S)-phenylthio-L-proline. In this report, an efficient hydrolytic resolution via Candida antarctic lipase B (CALB) for preparing the former block in isopropyl ether (IPE) containing (RS)-3-benzoylthio-2-methylpropyl pyrazolide (1) and water was developed. Quantitative improvements of the enzyme activity and enantioselectivity in terms of k2SKmS?1?=?5.726?L h?1 g?1 and E?=?217 at 45?°C were found from the kinetic analysis. Insights into the CALB performance via thermodynamic analysis were then addressed and compared with those by using (RS)-3-benzoylthio-2-methylpropyl 1,2,4-triazolide (2) as the substrate. A putative thermodynamic model was moreover hypothesised for elucidating the more enthalpy reduction of 68.92-70.86?kJ mol?1 from the acyl part of (S)-1 and (S)-2 as well as that of 23.69-25.63?kJ mol?1 from the triad imidazolium to Ser105 and leaving 1,2,4-triazole moiety of (R)-2 and (S)-2 on stabilising the corresponding transition states. 相似文献
4.
5.
Summary. Resveratrol (3,4′,5-trihydroxy-trans-stilbene) is a naturally occurring phytoalexin and polyphenol existing in grapes and various other plants, and one of the
best known ‘nutriceuticals’. It shows a multiplicity of beneficial biological effects, particularly, by attenuating atherogenic,
inflammatory, and carcinogenic processes. However, despite convincing evidence from experimental and clinical studies, data
concerning the role of resveratrol and other members of the large polyphenols family for human health is still a matter of
debate. One reason for this is the lack of suitable sensitive and specific methods, which would allow direct assessment of
biodistribution, biokinetics, and the metabolic fate of these compounds in vivo. The unique features of positron emission tomography (PET) as a non-invasive in vivo imaging methodology in combination with suitable PET radiotracers have great promise to assess quantitative information on
physiological effects of polyphenols in vivo. Herein we describe the radiosynthesis of an 18F-labelled resveratrol derivative, 3,5-dihydroxy-4′-[18F]fluoro-trans-stilbene ([18F]-1), using the Horner-Wadsworth-Emmons reaction as a novel radiolabelling technique in PET radiochemistry for subsequent functional
imaging of polyphenol metabolism in vivo. In a typical “three-step/one-pot” reaction, 18F-labelled resveratrol derivative [18F]-1 could be synthesized within 120–130 min including HPLC separation at a specific radioactivity of about 90 GBq/μmol. The radiochemical
yield was about 9% (decay-corrected) related to [18F]fluoride and the radiochemical purity exceeded 97%. First radiopharmacological evaluation included measurement of biodistribution
ex vivo and positron emission tomography (PET) studies in vivo after intravenous application of [18F]-1 in male Wistar rats using a dedicated small animal PET camera with very high spatial resolution. Concordantly with data on
bioavailability and metabolism of native resveratrol from the literature, these investigations revealed an extensive uptake
and metabolism in the liver and kidney, respectively, of [18F]-1. This study represents the first investigation of polyphenols in vivo by means of PET. 相似文献
6.
Keiichi Aritomo Chihiro Urashima Takeshi Wada Mitsuo Sekine 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):1-16
Abstract Reaction of 2′,3′,5′-O-silylated inosine derivative 1 with 2, 3-O-isopropylidene-5-O-tritylribosyl chloride (3) in a two-phase (CH2Cl2-aq. NaOH) system in the presence of Bu4NBr gave three products, i. e., 6-O-α-, 6-O-β-, and N 1-β-isomers of glycosides 4, 5a, and 5b. A similar PTC reaction of 1 with 2, 3, 5-tri-O-benzylribosyl bromide (9) gave four regio- and stereo-isomers involving the N1-β-glycoside 10. Reaction of 1 with 2, 3, 5-tri-O-benzoylribosyl bromide (11) afforded three products involving the desired N1-β-glycoside 12b, which could be deprotected to give N 1-ribosylinosine (15b) as a useful intermediate for the synthesis of cIDPR. 相似文献
7.
The sorptive behavior of bacteria—iron oxide composites was investigated in batch metal sorption assays using ferrihydrite in isolation (0.13 and 0.14 g/L ferrihydrite in cadmium and lead systems, respectively) as well as in combination with Bacillus subtilis (0.25 g/L adsorbent mixture) and Escherichia coli (0.27 g/L adsorbent mixture). A pH range from 3.0 to 6.5 was studied using total metal concentrations of 1.0 × 10 ? 4.0 and 3.2 × 10 ? 5 M with adsorbent mixtures proportioned on a 1:1 mass/volume basis. The log of the apparent surface complex formation constants (log K S M ) and sorption capacity (S max ) values were determined by fitting the experimental data to one-site Langmuir sorption isotherms. The one-site model effectively described the sorption data (r 2 > 0.9), where Cd 2 + exhibited somewhat lower sorption affinities (log K S M = ?3 for ferrihydrite, ?1.7 for B. subtilis–ferrihydrite, and ?1.1 for E. coli–ferrihydrite) than Pb 2 + (log K S M = ?0.9 for ferrihydrite, ? 0.2 forB. subtilis–ferrihydrite, and –0.1 for E. coli–ferrihydrite). The corresponding S max values for Cd 2 + and Pb 2 + on ferrihydrite were 0.78 mmole/g and 1.34 mmole/g, respectively. For the B. subtilis–ferrihydrite composites, Cd 2 + and Pb 2 + S max values were lower at 0.29 mmole/g and 0.5 mmole/g, respectively. Similar values were determined for the E. coli–ferrihydrite composites (0.15 mmole/g and 0.68 mmole/g for Cd 2 + and Pb 2 + , respectively). The sorption of Cd 2 + and Pb 2 + by each of the sorbent systems exhibited a strong dependence on pH with sorption edges in the range of pH 4.0 to 7.3. The observed S max of the composites were lower than values predicted upon available site additivity (Cd 2 + B. subtilis ?ferrihydrite : 0.29 mmole/g (observed) < 0.57 mmole/g (calculated); Cd 2 + E. coli ?ferrihydrite : 0.15 mmole/g (observed) < 0.44 mmole/ g (calculated); Pb 2 + B. subtilis ?ferrihydrite : 0.5 mmole/g (observed) < 0.805 mmole/g (calculated); Pb 2 + E. coli –ferrihydrite : 0.68 mmole/g (observed) < 0.775 mmole/g (calculated)), implying that a masking of reactive surface sites by attachment had occurred between the bacteria and ferrihydrite. Electrophoretic mobility analysis indicated that the ferrihydrite surface properties dominate the net surface charge for each composite system with lesser contributions from the bacteria. 相似文献
8.
P. Ellneskog-Staam R. von Bothmer K. Anamthawat-Jónsson B. Salomon 《Plant Systematics and Evolution》2007,265(3-4):241-249
Genomic in situ hybridisation (GISH) and Southern genomic hybridisation were applied in order to gain further knowledge regarding generic
delimitation of the genus Hystrix as well as to clarify the genomes of the Hystrix species H. patula, H. longearistata, H. coreana, H. duthiei and H. komarovii. The hybridisation intensity of different genomic probes was compared among the Hystrix species and with other Triticeae species. The Southern- and GISH results confirm that H. patula contains the StH genome and show that H. komarovii most likely has a variant of this StH genome. The other Hystrix species under study, i.e. H. longearistata, H. coreana and H. duthiei, contain an Ns basic genome, and most probably two variants of this basic genome, Ns
1
Ns
2
. The genus Hystrix is thus not a monophyletic group of species. 相似文献
9.
Joseph B. Yavitt Nathan Basiliko Merritt R. Turetsky Anthony G. Hay 《Geomicrobiology journal》2013,30(8):641-651
Because recent patterns of permafrost collapse in boreal peatlands appear to enhance emissions of CH 4 to the atmosphere, we examined methanogenesis and methanogen diversity in peat soil from peatlands with and without permafrost in two peatland complexes situated in continental western Canada. Peat soil from the active layer of permafrost bogs had very low rates of CH 4 production (ca. 10 nmol g ?1 day ?1 ), and we were unable to PCR-amplify 16s rRNA gene sequences using Archaea-specific primers in four peat samples. Surface peat soil from continental bogs with no permafrost supported moderate rates of CH 4 production (20–600 nmol g ?1 day ?1 ), with maximum rates in soil located close to the mean water table level. Additions of ethanol stimulated CH 4 production rates, suggesting metabolic substrate limitations. Peat from internal lawns, which have experienced surface permafrost degradation in the past 150 years, had very rapid rates of CH4 production (up to 800 nmol g ?1 day ?1 ) occurring within the soil profile. Concomitant rates of anaerobic CO 2 production were greater in continental bogs (ca. 6 μmol g ?1 day ?1 ) than in internal lawns (ca. 4 μ mol g ?1 day ?1 ) or in permafrost bogs (2.8 μ mol g ?1 day ?1 ). Analysis of the 16s rRNA gene for Archaea in the continental bog indicated mostly sequences associate with Methanobacteriales and RC-I with a Methanosarcinaceae sequence in the deepest peat soil. In the internal lawn, Methanosarcinaceae were most common in peat soil with a Methanosaetaceae sequence in the deepest peat soil. This study showed that patterns of discontinuous permafrost and ongoing permafrost degradation in boreal regions create patchy soil environments for methanogens and rates of methanogenesis. 相似文献
10.
N. A. Shakil Manish K. Singh M. Sathiyendiran J. Kumar 《Archives Of Phytopathology And Plant Protection》2013,46(20):1958-1965
Microwave irradiation of 2-hydroxy chalcones under solvent-free conditions resulted in a “green-chemistry” procedure for the preparation of flavanones in good yields, using an unmodified household microwave oven and silica as solid support. By irradiation of 2-hydroxy chalcones with trifluoroacetic acid over silica gel, 11 known flavanones were prepared in high yields. The synthesised compounds were characterised using spectroscopic techniques, namely, 1H NMR, 13C NMR and IR, and screened for their antifungal activity in vitro against Sclerotium rolfsii and Rhizoctonia solani by poisoned food technique. The compounds tested were found to be more active against R. solani, whereas against S. rolfsii, moderate activity was observed, as evident from LC50 values. The most potent compound 2-(4-fluorophenyl)-2,3-dihydrochromen-4-one (4a) had LC50 value of 12.0 mg L?1 followed by 11, 11a, 3a, 9a, 8a, 10a and 10 having LC50 values 18.21, 18.3, 32.9, 50.7, 88.8, 118.8 and 119.7 mg L?1, respectively. 相似文献
11.
Frank Seela Harald Debelak Hans Reuter Guide Kastner Igor A. Mikhailopulo 《Nucleosides, nucleotides & nucleic acids》2013,32(4):729-744
Abstract The 2′-O-methyl (2) and the 3′-O-methyl (3) derivatives of 1-deazaadenosine (1) were prepared. Single crystal X-ray analysis as well as 1H and 13C NMR studies were performed on the 3′-O-methyl-1-deazaadenosine 3. In the solid state, the glycosyl torsion angle (χ = 64.7°) is in the syn-range which is caused by an intramolecular (5′)CH2OH…N(3) hydrogen bond. The ribofuranose moiety adopts a 2 E (C-3′-exo; S) conformation and the orientation of the exocyclic C(4′)-C(5′) bond is + sc (γ(+)g). The conformation in solution was found to be very similar to that in solid state. Whereas the 2′-O-methyl derivative of 1 is a strong inhibitor of adenosine deaminase the 3′-O-methyl derivative is neither inhibitor nor substrate. 相似文献
12.
Lukas K. Filak Gerhard Mühlgassner Michael A. Jakupec Petra Heffeter Walter Berger Vladimir B. Arion Bernhard K. Keppler 《Journal of biological inorganic chemistry》2010,15(6):903-918
The synthesis of ruthenium(II) and osmium(II) arene complexes with the closely related indolo[3,2-c]quinolines N-(11H-indolo[3,2-c]quinolin-6-yl)-ethane-1,2-diamine (L
1
) and N′-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (L
2
) and indolo[3,2-d]benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-ethane-1,2-diamine (L
3
) and N′-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N,N-dimethylethane-1,2-diamine (L
4
) of the general formulas [(η6-p-cymene)MII(L
1
)Cl]Cl, where M is Ru (4) and Os (6), [(η6-p-cymene)MII(L
2
)Cl]Cl, where M is Ru (5) and Os (7), [(η6-p-cymene)MII(L
3
)Cl]Cl, where M is Ru (8) and Os (10), and [(η6-p-cymene)MII(L
4
)Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass
spectrometry, spectroscopy (IR, UV–vis, and NMR), and X-ray crystallography (L
1
·HCl, 4·H2O, 5, and 9·2.5H2O). Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells as well as cyclin-dependent
kinase (cdk) inhibition and DNA intercalation in cell-free settings have been established. The metal-free indolo[3,2-c]quinolines inhibit cancer cell growth in vitro, with IC50 values in the high nanomolar range, whereas those of the related indolo[3,2-d]benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of
cdk2/cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L
1
and 7 are not paralleled by a substantially higher kinase inhibition compared with indolobenzazepines L
4
and 11, arguing for additional targets and molecular effects, such as intercalation into DNA. 相似文献
13.
Ashty Saleh Frans Compernolle Gerard Janssen 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):689-692
Abstract We report an improved synthesis of N 6-(6-aminohexyl)FAD (1) using an efficient one-pot conversion of inosine to the N-trifluoroacetyl protected N 6-(6-aminohexyl)adenosine 3. The 5′-O-phosphorylated AMP derivative 4, activated as the imidazolide, was coupled with commercial sodium riboflavin phosphate by using 18-crown-6 in DMF. 相似文献
14.
Abrunhosa L Costa M Areias F Venâncio A Proença F 《Journal of industrial microbiology & biotechnology》2007,34(12):787-792
The activity on Aspergillus spp. growth and on ochratoxin A production of two novel chromene dimers (3) was evaluated. The results of the bioassays indicate that the chromene dimer 3a inhibited mycelia growth by approximately 50% (EC50) at 140.1 μmol L−1 for A. niger, 384.2 μmol L−1 for A. carbonarius, 69.1 μmol L−1 for A. alliaceus and 559.1 μmol L−1 for A. ochraceus. When applied at concentrations of 2 mmol L−1, 3a totally inhibited the growth of all Aspergillus spp. tested. Furthermore, ochratoxin A production by A. alliaceus was reduced by about 94% with a 200 μmol L−1 solution of this compound. A moderate inhibitory effect was observed for the analogous structure 3b on ochratoxin A production but not in mycelia growth. No inhibition was registered for compounds 2a and 2b, used as synthetic precursors of the dimeric species 3. 相似文献
15.
Michael Gütschow Markus Pietsch Andrea Themann Janine Fahrig Bärbel Schulze 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):341-347
A series of substituted 2,4,5-triphenylisothiazol-3(2H)-one 1,1-dioxides 9 was synthesized and investigated as inhibitors of human leukocyte elastase (HLE). All compounds were found to inhibit HLE in a time-dependent manner and most of them exhibited kobs/[I] values > 300 M? 1s? 1. The most potent 3-oxosultam of this series was 9l (kobs/[I] = 2440 M? 1s? 1). Kinetic investigations performed with 9g and different substrate concentrations did not allow to clearly distinguish between a competitive or noncompetitive mode of inhibition. A more complex interaction is supported by the failure of a linear dependency of kobs values on the inhibitor concentration. 相似文献
16.
Tokumi Maruyama Yoshiko Sato Takeshi Goto Mitsutoshi Fukuhara 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1079-1082
Abstract 2′,3′,5′-Tri-O(tetrahydropyran-2-yl)inosine 1 was treated with iodobenzene or 2-bromopyridine in the presence of cuprous oxide in pyridines to give the N1 -aryl derivatives 2a, b. Deprotection of the products afforded N1 -arylinosines 3a, b. 相似文献
17.
Chittanahalli N. Sudhamani Kalligundi R. Sangeetha Gowda Dugganna Girija Manju Giridhar 《Nucleosides, nucleotides & nucleic acids》2013,32(10):546-562
AbstractThe chemistry of Co(II) complexes showing efficient light induced DNA cleavage activity, binding propensity to calf thymus DNA and antibacterial PDT is summarized in this article. Complexes of formulation [Co(mqt)(B)2]ClO4 1–3 where mqt is 4-methylquinoline-2-thiol and B is N,N-donor heterocyclic base, viz. 1,10-phenanthroline (phen 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz 3) have been prepared and characterized. The DNA-binding behaviors of these three complexes were explored by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes 1, 2 and 3 were determined to be 1.6?×?103?M?1, 1.1?×?104?M?1 and 6.4?×?104?M?1 respectively. The experimental results suggest that these complexes interact with DNA through groove binding mode. The complexes show significant photocleavage of supercoiled (SC) DNA proceeds via a type-II process forming singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against E. coli and all complexes exhibited significant reduction in bacterial growth on photoirradiation. 相似文献
18.
Mohammed A. E. Sallam Leroy B. Townsend 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1215-1229
Abstract Treatment of 4-(D-gluco-pentitol-l-y1)-2-pheny1–2H-1,2,3-triazole (1) with p-toluenesulfonyl chloride in pyridine solution, afforded the homo-C-nucleoside analog, 4-(2,5-anhydro-D-gluco-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole (2) as well as its partial p-toluenesulfonyl derivative (3). 4-(5-Chloro-5-deoxy-D-gluco-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole (8), was isolated as a byproduct from the reaction. The structure and anomeric configuration of 2 was determined by acylation, 1H, 13C NMR, and NOE, spectroscopy as well as mass spectrometry. 相似文献
19.
Muhammad Amjad Sajjad H. Sumrra Muhammad Safwan Akram 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):88-97
AbstractMetal-based ethanolamines, (L1)–(L4) coordinated with Co(II), Cu(II), Ni(II) and Zn(II) metals in 1:2 (metal:ligand) molar ratio to produce new compounds have been reported. These compounds were screened for their bactericidal/fungicidal activity against a number of bacterial (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and Bacillus subtilis) and fungal strains (Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata) alongside against a shrimp species known as Artemia salina. The screening results indicated that metal complexes have significantly higher activity than uncomplexed ligands against one or more bacterial/fungal species due to chelation. The ligand (L4) displayed good bacterial and fungal activity as compared to other ligands. The antibacterial results revealed that the Zn(II) complex (16) of (L4) was found to be the most active complex and Co(II) complex (14) of the same ligand (L4), demonstrated the highest antifungal activity. 相似文献
20.
Squires RF Ai J Witt MR Kahnberg P Saederup E Sterner O Nielsen M 《Neurochemical research》1999,24(12):1593-1602
1. The bark of the root and stem of various Magnolia species has been used in Traditional Chinese Medicine to treat a variety of disorders including anxiety and nervous disturbances. The biphenolic compounds honokiol (H) and magnolol (M), the main components of the Chinese medicinal plant Magnolia officinalis, interact with GABAA receptors in rat brain in vitro. We compared the effects of H and M on [3H]muscimol (MUS) and [3H]flunitrazepam (FNM) binding using EDTA/water dialyzed rat brain membranes in a buffer containing 150 mM NaCl plus 5 mM Tris-HCl, pH 7.5 as well as [35S]t-butylbicyclophosphorothionate (TBPS) in 200 mM KBr plus 5 mM Tris-HCl, pH 7.5. H and M had similar enhancing effects on [3H]MUS as well as on [3H]FNM binding to rat brain membrane preparations, but H was 2.5 to 5.2 times more potent than M. 2. [
3
H]FNM binding. GABA alone almost doubled [3H]FNM binding with EC50 = 450 nM and 200 nM using forebrain and cerebellar membranes, respectively. In the presence of 5 M H or M the EC50 values for GABA were decreased to 79 and 89 nM, respectively, using forebrain, and 39 and 78 nM, using cerebellar membranes. H and M potently enhanced the potentiating effect of 200 nM GABA on [3H]FNM binding with EC50 values of 0.61 M and 1.6 M using forebrain membranes, with maximal enhancements of 33 and 47%, respectively. Using cerebellar membranes, the corresponding values were 0.25 and 1.1 M, and 22 and 34%. 3. [
3
H]MUS binding.
H and M increased [3H]MUS binding to whole forebrain membranes about 3-fold with EC50 values of 6.0 and 15 M. Using cerebellar membranes, H and M increased [3H]MUS binding ~68% with EC50 values of 2.3 and 12 M, respectively. Scatchard analysis revealed that the enhancements of [3H]MUS binding were due primarily to increases in the number of binding sites (Bmax values) with no effect on the high affinity binding constants (Kd values). The enhancing effect of H and M were not additive. 4. [
35
S]TBPS binding.
H and M displaced [35S]TBPS binding from sites on whole rat forebrain membranes with IC50 values of 7.8 and 6.0 M, respectively. Using cerebellar membranes, the corresponding IC50 values were 5.3 and 4.8 M. These inhibitory effects were reversed by the potent GABAA receptor blocker R5135 (10 nM), suggesting that H and M allosterically increase the affinity of GABAA receptors for GABA and MUS by binding to sites in GABAA receptor complexes. 5. Two monophenols, the anesthetic propofol (2,6-diisopropylphenol, P) and the anti-inflammatory diflunisal (2,4-difluoro-4-hydroxy-3-biphenyl carboxylic acid, D) also enhanced [3H]MUS binding, decreased the EC50 values for GABA in enhancing [3H]FNM binding and potentiated the enhancing effect of 200 nM GABA on [3H]FNM binding, although enhancements of [3H]MUS binding for these monophenols were smaller than those for H and M, using forebrain and cerebellar membranes. The enhancing effect of P and D on [3H]MUS binding were almost completely additive. 2,2-biphenol was inactive on [3H]MUS and [3H]FNM binding. These, and other preliminary experiments, suggest that appropriate ortho (C2) and para (C4) substitution increases the GABA-potentiating activity of phenols. 6. The potentiation of GABAergic neurotransmission by H and M is probably involved in their previously reported anxiolytic and central depressant effects. 相似文献