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p-Aminobenzoic acid derivatives as acetylcholinesterase inhibitors.

Because Alzheimer's disease (AD) is a medical problem characterized by progressive loss of memory and cognition that is associated with a deficient cholinergic system, this work aims to evaluate some p-aminobenzoic acid (PABA) derivatives as acetylcholinesterase inhibitors in vitro, in continuation with our last studies. The assayed compounds are low toxic, simple-structured and low cost.

4-Aminobenzoic Acid↗

The anti-endotoxic effect of o-aminobenzoic acid from Radix Isatidis.

AIM: To study the anti-endotoxic effect of o-aminobenzoic acid (OABA) isolated from Banlangen(BLG). METHODS: OABA was extracted and isolated from BLG and diluted into 0.5% solution. The concentration of endotoxin (ET) pretreated with OABA was quantitatively detected using Limulus test. The inhibition of ET-induced fever by OABA was measured in rabbits. The rates of lipopolysaccharides (LPS)-induced death in mice pretreated with or without OABA were then compared. The influence of OABA on the release of TNF-alpha and NO from macrophages induced by LPS was examined in mice. RESULTS: After pretreatment with OABA, 84.4% of ET was destroyed. The ET-induced fever in rabbits decreased significantly and the rate of LPS-induced death in mice dropped from 70% to 20%. The release of TNF-alpha and NO induced by LPS in mice was inhibited dose-dependently when the concentration of OABA was between 0.125% and 0.5%. CONCLUSION: OABA isolated from BLG has an anti-endotoxic effect.

Animals↗

N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase beta (human meprinbeta). A 13-amino-acid sequence is required for proteolyticprocessing and subsequent secretion.

N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase or human meprin (PPH) is a brush-border membrane enzyme of small intestinal epithelial cells. It is a type I integral membrane protein composed of two disulphide-bridged subunits (alpha and beta). PPH and its homologous counterparts in rodents belong to the astacin family of zinc-metalloendopeptidases. Although the amino-acid sequence of the beta subunits is 80-90% identical in these three species, processing is different. Expression of PPHbeta in simian virus 40-transformed African green monkey kidney cells (COS-1) and Madin Darby canine kidney (MDCK) cells results in its cell surface localization and secretion, whereas mouse meprinbeta is only found at the plasma membrane. To investigate proteolytic processing of PPHbeta and to identify the cleavage site, different C-terminal domains of wild-type PPHbeta were exchanged with the homologous domains of mouse meprinbeta. We identified a 13-amino-acid sequence (QIQLTPAPSVQDL) necessary for cleavage and subsequent secretion of PPHbeta. Using brefeldin A, the site of processing was identified as being after passage through the Golgi compartment. Proteolytic processing of PPHbeta thus provides a means for secretion of alphabeta heterodimers.

Amino Acid Sequence↗

[Effect of para-aminobenzoic acid on the growth of Actinomyces viscosus].

OBJECTIVE: To examine the effects of para-aminobenzoic acid (PABA) on the growth of Actinomyces viscosus. METHODS: Different concentrations of PABA (10(-10)-10(-3) g/L) were each transferred to modified Carlsson medium. Actinomyces viscosus ATCC19246 grew in them. And the cultures were incubated at 37 degrees C anaerobically in the atmosphere of 80%N2, 10%H2, 10%CO2 for 48 h. Actinomyces viscosus OD values (lambda = 540 nm) were obtained with UV-1601. Colony forming unit (CFU) was established by growth of Actinomyces viscosus in culture when different concentrations of PABA (10(-10)-10(-3) g/L) were present. RESULTS: Different concentrations of PABA (10(-10)-10(-4) g/L) had different stimulating effects on the growth of Actinomyces viscosus (P < 0.05). But this kind of stimulating effect declined when PABA concentration was 10(-5) g/L, and as PABA (10(-3) g/L) was present, this kind of effect was missing. CONCLUSION: The phenomena indicated that PABA has stimulating effect on the growth of Actinomyces viscosus, particularly when PABA is at the concentration of 10(-6) g/L.

Actinomyces viscosus↗

Fluorescence study of conformational properties of melanotropins labeled with aminobenzoic acid.

The native hormone alpha-melanocyte-stimulating hormone (alpha-MSH) and its more potent analog [Nle(4),D-Phe(7)]alpha-MSH (NDP-alpha MSH), labeled at the amino terminal with the fluorescent aminobenzoic acid (Abz) isomers, were examined by fluorescence methods. We observed energy transfer between the tryptophan(9) residue acting as donor and Abz as acceptor, the transfer being more pronounced to the ortho-form of the acceptor. Within the hypothesis that different peptide conformations coexist in equilibrium during the fluorescence decay, we supposed that the intensity decay was modulated by an acceptor-donor distance distribution function f(r). From the time-resolved fluorescence experimental data, we recovered the distance distribution between Abz and Trp(9), using the CONTIN program, within the framework of the Förster resonance energy transfer model. The methodology proved to be useful to provide quantitative information about conformational dynamics of melanotropins and its dependency on the solvent. In aqueous medium, alpha-MSH has a broad Abz-Trp(9) distance distribution, reflecting the structural flexibility of the peptide. Three different distance populations could be identified in the labeled analog NDP-alpha MSH in water, indicating distinct conformational states for the synthetic peptide, compared with the native hormone. Measurements in trifluoroethanol resulted in the recovery of two Abz-Trp(9) distance populations, both for the native and the analog hormones, reflecting the decrease, induced by the solvent, of the conformational states available to the peptides.

4-Aminobenzoic Acid↗

Determination of p-aminobenzoic acid and its metabolites in rabbit plasma by high-performance liquid chromatography with fluorescence detection.

A simple, accurate and sensitive high-performance liquid chromatographic method with fluorescence detection was used for measuring plasma concentrations of p-aminobenzoic acid (PABA) and its three metabolites: p-acetaminobenzoic acid (PAABA), p-aminohippuric acid (PAHA) and p-acetaminohippuric acid (PAAHA). A Cosmosil MS-C18 column (250 x 4.6 mm, 5 microns) was used under temperature control at 40 degrees C. The mobile phase was H2O-CH3CN-CH3COOH (100:3:1, pH 4.0) with a flow-rate of 1.5 ml/min. The excitation and emission wavelengths for fluorescence detection were set at 270 and 350 nm, respectively. Plasma samples (200 microliters) were acidified by the addition of 150 microliters of 1 m HClO4 solution containing salicylic acid (SA) as the internal standard. After centrifugation, 30 microliters of the supernatant were injected onto the column. Using this method, PABA and its three metabolites could be determined within 25 min. Within the investigated concentration ranges of PABA (0.1-50 micrograms/ml), PAABA (0.2-50 micrograms/ml), PAHA (0.1-50 micrograms/ml) and PAAHA (0.5-50 micrograms /ml), good linearity (r > 0.99) for the standard curves was obtained. The validation of this method showed coefficient of variance (C.V.) that was well below 15% for all compounds. After intravenous (i.v.) administration of PABA (20 mg/kg) to rabbits (n = 7), PABA followed a one-compartment open model elimination with a half-life of 10.90 +/- 1.03 min. The mean half lives for PAABA, PAHA and PAAHA were 24.61 +/- 6.42, 12.81 +/- 6.04 and 11.27 +/- 2.77 min, respectively.

4-Aminobenzoic Acid↗

Auxotrophs of Plasmodium falciparum dependent on p-aminobenzoic acid for growth.

The isolation of auxotrophic strains of a parasite offers new opportunities for studying parasitology. We have isolated cloned lines of Plasmodium falciparum that, unlike the parent line from which they were derived, rely on exogenous p-aminobenzoic acid (PABA) for growth. Isolation involved random mutagenesis of a cloned line of P. falciparum and subsequent selection of PABA-dependent parasites. Both parent and PABA-dependent clones were analyzed for PABA uptake and synthesis. Each clone takes up comparable amounts of PABA from the medium. The parent line, clone 3D7, can synthesize PABA de novo, whereas the PABA-dependent clones cannot. The requirement of exogenous PABA for growth by the auxotrophic strains coupled with their inability to synthesize PABA indicates that normal parasite growth can be completely supported by either synthesis or salvage. This work further clarifies the relationship between the availability of PABA and success of the parasite, an issue of debate from classic studies showing reduced parasite load in individuals on milk-fed diets.

4-Aminobenzoic Acid↗

General and specific solvent effects in optical spectra of ortho-aminobenzoic acid.

We describe studies about solvent effects on the absorption and emission properties of o-aminobenzoic acid (o-Abz), interpreting the results within the framework of general and specific solute-solvent interactions. Measurements were performed in several solvents and analysis of the absorption and emission wavelengths were made based on Lippert's model for general solvent effects and on the use of different parameters to describe the ability of the solvent to promote specific interactions with the solute. We observed low sensitivity of the Stokes shift upon changes in the medium polarity, and large deviation from the linearity predicted by Lippert's equation when the solvents were characterized as Bronsted acid in the Kamlet-Taft pi* scale. Quantum yield and fluorescence lifetimes were best interpreted based on the AN+DN scale used to describe the electron donor/acceptor properties of the solvent. The results indicated that non-radiative deexcitation processes are favoured in solvents which promote the formation of intramolecular hydrogen bond, while interactions with electron acceptor solvents lead to enhancement of fluorescence.

Journal Article↗

Use of p-aminobenzoic acid to monitor compliance with prescribed dietary regimens during metabolic balance studies in man.

A new method is described for simultaneously monitoring compliance with prescribed-diet and urine-collection regimens during metabolic balance studies. It involves incorporation of the potassium salt of p-aminobenzoic acid (PABA) into provided foods and measurement of its extent of recovery in urine. A validation study was conducted in 10 healthy adults. During three consecutive 24-h periods, subjects consumed four foods per day that had each been supplemented with 72.0 mg PABA and also made complete urine collections. An additional 24-h urine collection was made by each subject for determination of baseline PABA excretion. The PABA was easily incorporated into the test foods and was not detected by taste. The recovery of the PABA in urine, determined by colorimetric assay, was 98.7 +/- 3.7% (means +/- SD) of intake. Thus, in metabolic studies for greater than or equal to 3 d, PABA can be used to provide a sensitive index of dietary compliance.

4-Aminobenzoic Acid↗

The use of P-aminobenzoic acid and chromic oxide to confirm complete excreta collection in a carnivore, Felis silvestris catus.

Complete excreta collection is a pre-requisite for several protocols in protein metabolism, and lack of confidence in achieving this may be increased when working with carnivores. Recovery of p-aminobenzoic acid (PABA) as a check for complete urine collection and chromic oxide for complete faeces collection were assessed in the cat. A single oral dose of PABA (4 mg/kg BW) was excreted more slowly than has been reported in the human (82% recovery at 6 h). A daily dose of PABA proved a useful method for confirming complete urine collection in the cat, and was 99% excreted in 72 h. Chromic oxide (500 mg/cat) was administered orally and recovery of chromium in the faeces was 90% after 96 h. A HPLC method for the analysis of PABA in cat urine was developed, and from the application of the techniques to a nitrogen balance study, it was concluded that PABA and chromic oxide are useful checks for complete excreta collection in the cat.

4-Aminobenzoic Acid↗

[Genetic activity of para-aminobenzoic acid. The intensification of DNA polymerase I-dependent repair induced by chemical mutagens in toluene-treated Escherichia coli cells].

Alkylatio of Escherichia coli DNA that have been made permeable to nucleotides by toluene treatment results in the expression of DNA polymerase I-directed repair synthesis. The system only permits measurement of DNA polymerase I-directed repair synthesis. The latter is not observed in mutant cells deficient in this polymerase. DNA ligation is intentionally prevented by the addition of the inhibitor, nicotinamide mononucleotide. MNU, ENU and MMS elicit DNA polymerase I-directed repair synthesis. MNU and MMS are especially potent in this regard, while EMS is a poor inducer of DNA polymerase I activity in permeabilized cells. The natural compound para-aminobenzoic acid itself (0,0002 mM - 20 mM) doesn't induce DNA polymerase I-directed repair synthesis. However, when PABA is used in complex with alkylating agents as the inducers, the repair synthesis increased 2,0, 1,2 and 2,8 times for MNU, ENU and EMS, respectively, as compared to that elicited by "pure" mutagens. The increasing of DNA repair synthesis in permeabilized bacteria in the experiments with PABA may serve as the foundation for its reparagenic activity. The latter was discovered previously by the authors in experiments on mutagenesis of bacterial cells.

4-Aminobenzoic Acid↗