bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial activity of extracts from some Canary species of Phaeophyta and Chlorophyta
Authors: Febles C. I. , Arias A. , Hardisson A. , López A. Sierra , Gil‐Rodríguez M. C. 
Published: October 2006

AbstractA number of brown (Phaeophyta) and green (Chlorophyta) seaweeds have been collected from the littoral of Tenerife (Canary Islands) and extracts from them have been studied for antibacterial and antifungal activity.Three different solvents, n‐hexane, ethyl acetate and methanol have been used to obtain extracts from the Phaeophyta: Sargassum desfontainesii (Turner) C. Agardh, Halopteris scoparia (Linnaeus) Sauvageau and Stypopodium zonale (Lamouroux) Papenfuss; and the Chlorophyta: Codium intertextum (Collins et Hervey) and Ulva rigida (Clemente) C. Agardh. The activity of the extracts was tested using Gram‐positive, Gram‐negative bacteria and yeasts. The methanol extract showed most antibacterial activity. The extracts were mainly active against bacteria (Gram +) while all the fungi tested proved to be resistant to the extracts of brown seaweeds, however, the methanol extract of Codium intertextum (Chlorophyta) showed considerable action against some yeasts tested.
A double‐blind study with a new monodrug Kan Jang: Decrease of symptoms and improvement in the recovery from common colds
Authors: Hancke Juan , Burgos Rafael , Caceres Dante , Wikman Georg 
Published: October 2006

AbstractIn a placebo‐controlled double‐blind study, the therapeutic effect of Kan Jang tablets made from Andrographis paniculata (Barm. F.) (Ness) dried extract was tested in patients with common colds. The patients were divided in two groups, in which group 1 (n = 33) received 1200 mg of Andrographis paniculata and group 2 (n = 28) a placebo (P).On day 3–4 after treatment the possible effect of Kan Jang tablets on selected symptoms and clinical signs of common cold was evaluated. A significant reduction in clinical symptoms at day 4 of administration of the Kan Jang tablets was observed. A better efficacy against the placebo is discussed.The differences in the total ‘sumscores’ of clinical and symptomatic findings indicate that the Kan Jang treated group did far better than the placebo group. We conclude that Kan Jang in a dose of 1200 mg daily has the capacity to significantly shorten the course/duration of the disease and therefore is indicated for an enhanced resistance to common colds.
Clinical evaluation of lecithin as a lipid‐lowering agent
Authors: Wójcicki J. , Pawlik A. , Samochowiec L. , Kaldoǹska M. , Myśliwiec Z. 
Published: October 2006

AbstractThe purpose of this investigation was to measure plasma lipid composition following oral administration of soybean lecithin in 32 patients with primary hyperlipidaemia. Lecithin granulate (Sternpur) was given for 30 days. Before starting the treatment and after 30 days of mangement blood was taken to establish the lipid concentration. Mean total cholesterol concentration was significantly decreased by 33%, while LDL‐level was diminished by 38%. HDL‐cholesterol concentration at the same time was increased significantly by 46%. Mean triglyceride concentration in these persons was significantly decreased by 33%. In conclusion, lecithin, a preparation obtained from soya, should be administered for the prevention and treatment of atherosclerosis.
Cochlospermum planchonii rhizome extract with hepatoprotective activity inhibits cytochrome P‐450 monooxygenases
Authors: Aliyu Roseline , Okoye Z. S. C. , Shier W. Thomas 
Published: October 2006

AbstractAn aqueous extract of Cochlospermum planchonii rhizomes prepared in the manner used by native medical practitioners in northern Nigeria to treat jaundice protects CCI4‐treated rats from liver damage measured as elevated serum levels of diagnostic enzymes. The extract inhibits cytochrome P‐450 monoxygenases aminopyrine‐N‐demethylase and aniline hydroxylase, suggesting a plausible hepatoprotective mechanism.
Development and evaluation of antimicrobial natamycin‐incorporated film in gorgonzola cheese conservation
Authors: de Oliveira Talita Moreira , de Fátima Ferreira Soares Nilda , Pereira Rodrigo Magela , de Freitas Fraga Kátia 
Published: October 2006

AbstractConservation of food products depends on product quality and packaging suitability. The objective of this work was to develop and evaluate the antimicrobial efficiency of natamycin‐incorporated film in the production process of Gorgonzola cheese. It aims to optimize the production process and increase shelf‐life and food safety for the consumer. Films with different concentrations of natamycin were produced and tested in Gorgonzola cheeses to evaluate its efficiency against Penicillium roqueforti on the cheese surface. Films with 2 and 4% natamycin presented satisfactory results for fungus inhibition and the amount of natamycin released to the cheese was below that allowed by the legislation. Copyright © 2006 John Wiley & Sons, Ltd.
Multivariate Data Analysis of Various Biological Test Systems Used for the Quantification of Ecotoxic Compounds
Authors: Nendza M. , Seydel J. K. 
Published: October 2006

AbstractThe toxic effects of ecotoxicologically relevant chemicals (phenols, anilines, aliphatic hydrocarbons) have been determined using several in vitro testing procedures which are assumed to represent relevant biological systems. These test systems selected within a collaborative study supply information about toxic effects on different levels of interference with ecosystems. Other selection criteria were reliability of the procedures, exact quantification of the observed effects, and low cost. Subsequently the toxicity data obtained in the different biological systems for more than 50 phenol‐, aniline derivatives and hydrocarbons were used to derive quantitative structure‐toxicity relationships. The regression equations obtained were compared. For all biosystems under study a dependence of toxic potency on the lipophilic properties of the compounds was found. With the same data set principal component analysis has been performed and the results give evidence that the ranking of toxicants is similar in the different testing systems used.These results are further supported by the analysis of literature data from test systems of various complexity.
Quantitative Structure‐Activity Study of the Inhibition of Acetylcholinesterase with Aliphatic Ammonium Ions
Authors: Takayama Chiyozo , Akamatsu Miki , Fujita Toshio 
Published: October 2006

AbstractTo understand the role of the interaction between the positively charged quaternary nitrogen of the acetylcholine molecule and the anionic site of acetylcholinesterase, we measured the affinity of a number of aliphatic ammonium ions with bovine erythrocyte acetylcholinesterase in terms of the inhibition constant Ki and quantitatively analyzed the affinity index, log (1/Ki), with free‐energy‐related substituent and structural parameters and the multiple regression technique. Since the interaction of ammonium ions with the anionic site is regarded as being a type of ion‐pair formation in a hydrophobic milieu, we expected that the total steric effect of N‐substituents should be similar to that previously studied for the ion‐pair formation‐partition equilibrium of ammonium ions with picrate in the 1‐octanol/water system. By taking all of the steric effect terms in this ion‐pairing system as a single independent variable, the analysis was made to separate the specific hydrophobic effect of four N‐substituents on the affinity from their steric effect. The ammonium ions were suggested to interact with the anionic site so that the hydrophobic interaction of N‐substituents is dependent on their relative size while the total steric congestion is lowest. The hydrophobic nature of the enzymic milieu surrounding the anionic site was not uniform. The NH hydrogens in ions other than the quaternary were shown to lower the inhibitory activity nearly in proportion to their number. Being hydrated, the positively charged NH group could work to hold the ions in the bulk aqueous phase rather than on the enzyme.
Relationships Between Octanol/Water Partition Coefficients and Total Molecular Surface Area and Total Molecular Volume of Hydrophobic Organic Chemicals
Authors: de Bruijn Jack , Hermens Joop 
Published: October 2006

AbstractRelationships between octanol/water partition coefficients (Kow) and parameters for molecular surface area or molecular volume are examined with new Kow data determined by the slow‐stirring method. It is shown that Kow values of chlorobenzenes (PCBz's) and polychlorinated biphenyls (PCBs) can be described well using a single parameter regression equation. However, separate equations are established for the different groups of compounds. For 18 PCBs a very significant equation was obtained using data for the solvent accessible surface area (SASA) that was calculated according to a full quantum chemical geometry optimization of the chemicals. With a corrected shorthand method for the calculation of the total molecular surface area (TSA) or volume (TMV), also very significant relationships were obtained.An attempt was made to combine the Kow data for both PCBz's and PCBs within one equation by adding the solvatochromic parameters. However, there remained differences between the experimental and calculated results for the chlorobenzenes and the PCBs.All linear correlations showed a deflection from the calculated values at high molecular areas or volumes which is probably caused by a solubilizing effect of the octanol present in the aqueous phase. Based on these observed deflections we estimate that the octanol/water partition coefficient (log Kow) will not exceed a value of 9.
Determination of Productive Conformation of Acetylcholinesterase Substrates Using Molecular Mechanics
Authors: Zhorov Boris S. , Shestakova Natalya N. , Rozengart Evgeniy V. 
Published: October 2006

AbstractAll equilibrium conformations (conformers) of 23 acetylcholinesterase substrates, conformationally flexible or semirigid derivatives of acetylcholine, were calculated using molecular mechanics. In a series of α‐alkyl‐β‐alkyl derivatives of acetylcholine, a correlation was found between the rate of hydrolysis of substrates and population of their completely extended tt‐conformers. Among cyclic analogs of acetylcholine, only those substrates which are compatible with the tt‐conformer of acetylcholine by the spatial disposition of the ammonium group, carbonyl oxygen and carbonyl carbon, are hydrolyzed at a high rate. In acetylcholine derivatives with elongated chain between acetyl and cationic groups, the hydrolysis rate varies directly with the population of conformers compatible with the tt‐conformer of acetylcholine. It is concluded that the tt‐conformer of acetylcholine is productive for the hydrolysis by acetylcholinesterase.
Comparative Molecular Field Analysis on a Set of Muscarinic Agonists
Authors: Greco Giovanni , Novellino Ettore , Silipo Carlo , Vittoria Antonio 
Published: October 2006

AbstractA three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) was carried out on a set of 39 non‐congeneric muscarinic agonists using Comparative Molecular Field Analysis (CoMFA). The compounds were tested on the M3 receptor subtype. However, since most of these ligands are reported as unspecific muscarinic agents, the proposed pharmacophore model accounts for features common to all the receptor populations (M1, M2 and M3). In order to define an alignment rule for the superimposition of the ligands, a common pharmacophore frame was derived with a preliminary conformational search performed on four typical muscarinic agonists. Both the steric and the electrostatic fields were used in CoMFA as molecular descriptors and were found relevant with almost the same statistical weight. The CoMFA coefficient contour maps revealed consistency with our postulated mechanism of interaction.Several 3D‐QSARs were derived by means of the Partial Least Squares (PLS) method choosing the proper dimensionality with a cross‐validation procedure.
Theoretical Prediction of Antigenic Determinants Based on Protein‐Water Interaction Energies
Authors: Hofmann Hans‐Jörg , Hädge Dietlind , Höltje Monika , Höltje Hans‐Dieter 
Published: October 2006

AbstractGoodford's GRIN/GRID method is used for the prediction of protein antigenic determinants by calculation of the interaction energy between proteins and water. The comparison of the regions of high interaction energy for the proteins lysozyme, myohemerythrin and tobacco mosaic virus protein with experimentally determined contact surfaces in antigen‐antibody complexes and epitopes obtained by cross‐reactivity measurements shows remarkable agreement. Accessible surface regions of considerable attraction for polar probes seem to be of special importance for antigen‐antibody recognition.
Structure‐activity Relations in Gestagenic Steroids by the MTD Method. The Case of Hard Molecules and Soft Receptors
Authors: Simon Z. , Bohl M. 
Published: October 2006

AbstractA QSAR is obtained for affinity towards the gestagenic receptor for a series of 55 progesterone derivatives (r = 0.935), using the MTD‐method, with MTD for steric misfit and f a corrected relative hydrophobicity. Acceptable stability of regression coefficients of vertex attributions are obtained when this QSAR is compared with previous QSAR's for a reduced series of progesterone derivatives and for testosterone derivatives. Acceptable predicted activities for test molecules (r2 = 0.71) and acceptable results in a cross validation‐like procedure (r2 = 0.76) were obtained. These are strong arguments that our MTD results correspond to some real features of the gestagenic receptor site. In order to explain relative success of the MTD‐method in QSAR's for steroids, as compared to other methods, molecular aspects of the receptor‐effector interaction are discussed in relation to QSAR‐methodology. Recent computational chemistry approaches are based upon drug molecule‐receptor site energy calculations, assuming a fixed conformation for the receptor site. If the drug molecules are “hard” (rigid), the steric misfit with a “soft” (conformationally flexible) receptor site may be avoided by induction of different local conformational changes in the latter.
Drug Lipophilicity in QSAR Practice: II. Aspects of RM‐Determinations; Critics of RM‐Corrections; Interrelations with Partition Coefficients
Authors: Dross Karl P. , Mannhold Raimund , Rekker Roelof F. 
Published: October 2006

AbstractExperimental conditions for the derivation of precise RM‐values are examined; the importance and the theoretical background of the extrapolation to modifyer‐free conditions as well as the generally proposed pK‐correction for RM are discussed. Compounds included in this study stem from the following four classes of drugs: antiarrhythmics, β‐blockers, phenothiazines and benzamides.RM‐values of these compounds (determined in acetonitrile/buffer) are compared with experimentally determined (log Pobs, log P*) as well as calculated log P values (∑f, C log P). Best interrelation is found with non‐pK corrected data derived in a buffer to modifyer mixture 50/50. Comparison of the calculative approaches indicates a slight superiority of ∑f over C log P.
An Interaction Model for Tiotidine and Analogues with the Histamine H2‐Receptor
Authors: Haaksma Eric E. J. , Voss Hans‐Peter , Den Kelder Gabriëlle M. Donné‐Op , Timmerman Hendrik 
Published: October 2006

AbstractFor studying the interaction of compounds with a receptor it is important to have a pharmacophoric model which describes the possible sites of interaction. The high flexibility of H2‐antagonists such as cimetidine, ranitidine and tiotidine hampered the definition of such a 3D interaction model for the H2‐receptor. However, for tiotidine a number of analogues are known which do not only have different substituents at various parts of the molecule, but which are rigid as well. This makes these compounds suitable for the purpose of defining a pharmacophoric model. Based upon a comparison of the various tiotidine analogues it was possible to determine four sites of interaction. Two receptor binding sites interact with the two NH2 groups present in the 2‐guanidine group of tiotidine. The third site at the receptor interacts with the NH2 group of the cyanoguanidine moiety which is connected to the ethylthiomethyl chain; this NH2 group functions as a proton donor. The fourth binding site was found via a tiotidine analogue in which the flexible side chain had been replaced by a 4(5) imidazole group. One of the nitrogens of this imidazole ring functions as a proton donor. The orientation of this proton donor parallels the orientation of the proton donor function present in the cyanoguanidine group of tiotidine itself, leading to the suggestion that these two proton donor functions interact with the same receptor site. The results from these structural considerations, are summarized in a schematic model that can be used for subsequent studies on different groups of H2‐antagonists.
The History of Drug Research: From Overton to Hansch
Authors: Rekker Roelof F. 
Published: October 2006

AbstractThe paper overviews part of the history of Drug Research, the period from Overton to and including Hansch, and pays special attention to the development of parameter sets describing electronic, lipophilic and steric substituent effects. Extra emphasis is given to the evolution in the methodology of log P calculation. The sequence of π, f (Rekker – original), f (Hansch), f (Rekker – revised) is not yet closed but open for further developments, such as development of hydrophobic fragmental sets especially designed for the study of blood‐brain barrier transfer.
Modelling the Cytotoxicity of Halogenated Aliphatic Hydrocarbons. Quantitative Structure‐Activity Relationships for the IC50 to Human HeLa Cells
Authors: Eriksson Lennart , Sandström Björn E. , Sjöström Michael , Tysklind Mats , Wold Svante 
Published: October 2006

AbstractThe cytotoxicity towards human HeLa cells has been determined for a series of halogenated aliphatic hydrocarbons. The cytotoxicity, expressed as the inhibitory concentration lowering cell viability by 50%, IC50, is modelled by means of calculating a multivariate quantitative structure‐activity relationship based on a training set comprising ten chemicals. It is shown that the cytotoxicity of the compounds critically depends on their hydrophobic and steric properties. The QSAR is validated by making predictions for an external validation set consisting of six substances. In this context, a comparison between internal validation, that is crossvalidation, and external validation of the predictability of a QSAR, is made. The results obtained indicate that the latter method is the more demanding and likely leads to a model exhibiting optimal predictive power. Subsequently, the validated QSAR is also used for making predictions for 40 non‐tested compounds of similar chemical properties. The question of variable selection in the context of QSAR calculations is also addressed. Finally, the cytotoxicity endpoint is multivariately related to eight other biological variables for the training set compounds. This, so called, multivariate biological profiling, indicates that the cytotoxicity endpoint mediates information not conveyed by the other eight variables.
The Probability of Chance Correlation Using Partial Least Squares (PLS)
Authors: Clark Matthew , Cramer Richard D. 
Published: October 2006

AbstractThe frequency of chance correlation using partial least squares (PLS) has been measured experimentally for variously dimensioned data, comprising either completely random numbers, random numbers containing a perfect correlation within, and CoMFA field descriptors. This frequency, much lower than that for stepwise multiple regression, is maximal for datasets in which the number of descriptors equals the number of compounds, and surprisingly decreases indefinitely as the number of descriptors becomes much greater than the number of compounds. However, perfect correlations involving descriptor subsets are not detected by PLS if the number of irrelevant descriptors is excessive. In CoMFA applications, the probability of chance correlation is usually negligible. For example with 21 compounds a crossvalidated r2 value greater than 0.25 will occur by chance in less than 5% of trials.
Multiconformational Minimal Steric Difference. Structure‐Acetylcholinesterase Hydrolysis Rates Relations for Acetic Acid Esters
Authors: Ciubotariu D. , Deretey E. , Oprea T. I. , Sulea T. , Simon Z. , Kurunczi L. , Chiriac A. 
Published: October 2006

AbstractThis note presents the multiconformational MTD method and its application in a QSAR for acetylcholinesterase catalysed hydrolysis rates of a series of 25 acetic acid esters. Multiconformational MTD allows consideration of molecules with several low energy conformations, as the mostly aliphatic alcohol esters of this series, for QSAR. Conformations were selected for the QSAR study according to their energies calculated by the COSMIC modelling program. Information from an X‐ray crystallography study, together with results of conformational energy calculations was used in constructing the hypermolecule for the 25 acetic acid ester molecules. A classical Hansch QSAR, with σ*‐Taft constants, π‐hydrophobicities and Es‐steric constants yields r2 = 0.779 and r2cv = 0.577 in a crossvalidation procedure. The multiconformational MTD, with σ* and MTD as structural parameters yields, for the corelational equation r2 = 0.868 and r2cv = 0.661 in a cross validation procedure. Both correlational equations indicate an appreciable positive effect of electron withdrawing ester groups. The optimised receptor map indicates a receptor cavity with certain similarities to acetylcholine, but somewhat larger. QSAR studies are able, thus, to yield supplementary details to those given by X‐ray studies.
The Generation of Molecular Structures from a Graph‐Based QSAR Equation
Authors: Kier Lemont B. , Hall Lowell H. 
Published: October 2006

AbstractThe concept of the generation of molecular structures directly from a QSAR equation using topological indices is presented. The equations relating the path counts to the graph atom degree counts is presented as a linkage in the flow of information. The multiple candidate molecules are derived from target indices using a quality QSAR equation. An example is developed to illustrate the process using molecular connectivity indices.
Analysis of Distance Matrices for Studying Data Structures and Separating Classes
Authors: Benigni R. , Giuliani A. 
Published: October 2006

AbstractThis paper demonstrates that the computation of Euclidian distances between objects generates an intrinsic geometry, which, besides containing all the information explicitly present in the original space, also provides new information about the object interrelationships. In other words, by computing distances the data are mapped onto a new, and more flexible, reference frame. Such properties of the distance function also permit the derivation of non linear descriptors of the data space, and can be usefully exploited for pattern recognition purposes. In particular, it is demonstrated that this approach is able to separate embedded classes, which have been repeatedly reported in QSAR research.