bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibacterial activity of flavanone isolated from Sophora exigua against methicillin‐resistant Staphylococcus aureus and its combination with antibiotics
Authors: Sato M. , Tsuchiya H. , Takase I. , Kureshiro H. , Tanigaki S. , Iinuma M. 
Published: October 2006

Abstract5,7,2′,4′‐Tetrahydroxy‐8‐lavandulyl‐flavanone, isolated from Sophora exigua, completely inhibited the growth of 21 strains of methicillin‐resistant Staphylococcus aureus (MRSA) at concentrations of 3.13–6.25 μg/mL. The anti‐MRSA effect was based on bactericidal action. In combinations of the flavanone with vancomycin, minocycline and rifampicin, the fractional inhibitory concentration indices were 0.90, 0.88 and 0.85, respectively, indicating partial synergistic effects with anti‐MRSA antibiotics. The proposed flavanone would be a potent phytotherapeutic agent against MRSA infections.
Protection against galactosamine and tert‐butyl hydroperoxide induced hepatocyte damage by Melothria maderaspatana extract
Authors: Thabrew M. Ira , Gove Christopher D. , Hughes Robin D. , McFarlane Ian G. , Williams Roger 
Published: October 2006

AbstractThe aqueous extract of Melothria maderaspatana is used by traditional medical practitioners to treat jaundice in man. The effect of Melothria maderaspatana extract on damage induced in freshly isolated rat hepatocytes by D‐galactosamine and tert‐butyl hydroperoxide (TBH) has been investigated. On incubation of hepatocytes with galactosamine or TBH in the presence of the plant extract, a significant dose‐dependent protection against hepatocyte damage was observed, with maximum protection at a concentration of 500 μg/mL. At this concentration the galactosamine‐induced release of lactate dehydrogenase (LDH) and aspartate amino‐transferase (AST) were reduced by 40.7% ± 4.2% and 37.7% ± 6.1% respectively, compared with control incubations. The TBH‐induced lipid peroxidation (estimated from malondialdehyde production) was decreased by 26.0 ± 3.7% together with a 38.4% ± 4.4% and 40.8 ± 7.6% reduction in the release of cellular LDH and AST respectively into the incubation medium. On post‐treatment with the plant extract the protective activity was found to decrease with increase in time of exposure of the cells to either of the toxins. The direct protective effects of Melothria extract on hepatocytes support the use of this plant as a herbal remedy.
Effects of Ganoderma lucidum on cellular immunocompetence in γ‐irradiated mice
Authors: Chen Wang‐Chi , Hau Dou‐Mong 
Published: October 2006

AbstractWe have investigated the effects on mice treated with Ganoderma lucidum (GI) when the whole body was exposed to 400 rad γ‐irradiation. The mice were divided into five groups. Group A was the normal control; group B, the experimental control, was treated with GI; group C was the radiation control (RT); group D was treated with RT and GI; group E was treated with GI, RT and GI. The results revealed that the relative spleen weight had increased significantly in groups B and E on day 7 and increased in all experimental groups on day 28 after irradiation. The leukocyte counts decreased obviously in groups C, D and E on day 7, and recovered in groups D and E was faster than that in group C on day 28. The blastogenic response of splenocytes to LPS, Con A and PHA in groups administered GI were higher than that in group C on days 7 and 28. Therefore, GI seemed to assist the recovery of cellular immunocompetence in γ‐irradiated mice.
Effects of Salvia lavandulifolia Vahl. ssp. Oxyodon extract on pancreatic endocrine tissue in streptozotocin‐diabetic rats
Authors: Jiménez I. , Jiménez J. , Gámez M. J. , González M. , De Medina F. Sánchez , Zarzuelo A. , Osuna I. 
Published: October 2006

AbstractWe have investigated the antidiabetic activity of Salvia lavandulifolia ssp. oxyodon extract on rats pancreotomized by streptozotocin (STZ). At a dose of 10 mg dry residue/kg the extract produced: an increase in Langerhans islet number and size; an increase in pancreatic insulin content. When both Salvia extract (10 mg/kg) and glibenclamide (1 mg/kg) were administered concurrently to STZ‐diabetic rats, a significant decrease in glycaemic level (>40%) and mortality index was achieved.
The analgesic‐antiinflammatory extract from Araujia sericifera lacks ulcerogenic activity on stress‐gastric damage model
Authors: Bello R. , Martínez‐Cuesta M. A. , Moreno L. , Esplugues J. , Primo‐Yúfera E. 
Published: October 2006

AbstractThe present study evaluates the ulcerogenic activity of the hexane extract from dry fruits of Araujia sericifera in an experimental model of cold‐restraint stress. Treatment of rats with 200 mg/kg (i.p.) of hexane extract did not affect the gastric lesions induced by cold‐restraint stress. However, it was confirmed that a dose of 300 mg/kg (i.p.) of acetylsalicylic acid (ASA) which induced a similar analgesic‐antiinflammatory effect, increased significantly the level of gastric damage. Thus, the hexane extract from the fruits of A. sericifera seems to possess analgesic‐antiinflammatory properties which are not linked to gastrolesive effects.
Synergistic effects of inchin‐ko‐to (Yin‐Chen‐Hao‐Tang) and ursodeoxycholic acid on cholestasis caused by α‐naphthyl isothiocyanate
Authors: Nomura Masaaki , Hida Tatsuhito , Miyamoto Ken‐Ichi , Ohshima Taeyuki , Hayashi Hisao , Sawanishi Hiroyuki 
Published: October 2006

AbstractThe effects of the combination of Inchin‐ko‐to, a kampo formulation, and ursodeoxycholic acid on experimental cholestasis were investigated. When administered intraduodenally at noneffective doses of these drugs to rats with intrahepatic cholestasis caused by α‐naphthyl isothiocyanate, the bile flow returned to a near‐normal level and the serum bile acid profile was improved. Among the major components of the kampo formula, Artemisiae capillaris Flos contributed to the change in the bile flow, and Gardeniae Fructus contributed to the improved serum bile acid profile, because ursodeoxycholic acid increased and cholic acid decreased. The results show that urosdeoxycholic acid and Inchin‐ko‐to synergistically improved experimental cholestasis and that this effect occurred because of different functions of the components of Inchin‐ko‐to.
Antiulcer activity of Tinospora cordifolia Miers and Centella asiatica linn extracts
Authors: Sarma D. N. K. , Khosa R. L. , Chansauria J. P. N. , Sahai M. 
Published: October 2006

AbstractThe ethanol extracts of the roots of T. cordifolia Miers and C. asiatica Linn were observed to induce a marked protective action against an 8 h restraint stress induced ulcerization, the activity being comparable to that of diazepam.
Comparative hepatoprotective activity of three Phyllanthus species, P. urinaria, P. niruri and P. simplex, on carbon tetrachloride induced liver injury in the rat
Authors: Prakash A. , Satyan K. S. , Wahi S. P. , Singh R. P. 
Published: October 2006

AbstractThe effect of alcohol extracts of three Phyllanthus species was compared on carbon tetrachloride‐induced (chronic) hepatic damage in rats. Alcohol extracts of P. niruri, P. urinaria and P. simplex were administered orally at three different doses. Statistically significant reversal of the elevated serum levels of transaminases (GOT and GPT) were used as the biochemical indices for hepatoprotection. The results of the study indicated that only the extracts of P. niruri and P. urinaria afforded protection of liver in the chronic model. The hepatoprotective activity of P. urinaria is about 60% in comparison with P. niruri. Therefore, P. urinaria may be considered as a good substitute for P. niruri in cases of liver disorders in actual practice.
On a Fragment Approach to Structure‐activity Correlations
Authors: Randić Milan , Jurs Peter C. 
Published: October 2006

AbstractIn searching for better structure‐activity correlations frequently one considers various fragments as the underlying key elements for improving the correlation. We address here the search for useful fragments and discuss some criteria for their selection. The approach, which is essentially a graph theoretical one, is based on characterization of fragments by suitably weighted paths. As an illustration we re‐examined the correlation between the antiviral activity of a series of alkyl substituted benzimidazoles and their structures represented by connectivity indices. Fragment path numbers provide an alternative representation which allows additional discussion and additional conclusions concerning QSAR applications.
Hydrogen Bonding 12. A New QSAR for Upper Respiratory Tract Irritation by Airborne Chemicals in Mice
Authors: Abraham Michael H. , Whiting Gary S. , Alarie Yves , Morris Jeffrey J. , Taylor Peter J. , Doherty Ruth M. , Taft Robert W. , Nielsen Gunnar D. 
Published: October 2006

AbstractUpper respiratory tract irritation of male Swiss OF1 mice by airborne chemicals is well correlated by the following equations for the toxicity of nonreactive compounds, magnified image FRD′50 is the concentration in mol 1−1 of the airborne chemical required to elicit a 50% decrease in respiratory rate, and the explanatory variables are δ2 a polarisability correction term, π the solute dipolarity, α the solute hydrogen‐bond acidity, Vx the characteristic volume, and L16 the gas/hexadecane partition coefficient. These equations considerably resemble corresponding equations for gas/liquid partition coefficients into organic bases such as tricresylphosphate, but do not resemble an equation for gas/water partition coefficients.
The QSAR Application of a New Steric Parameter Set for Aromatic Substituents Defined by the Acidic Hydrolysis Rate of Ortho‐substituted Benzamides
Authors: Sotomatsu Tomoko , Fujita Toshio 
Published: October 2006

AbstractWe examined applications of a new steric parameter set for aromatic substituents, Es(AMD), recently defined by the rate constants for acidic hydrolysis of ortho‐substituted benzamides, to the QSAR study of biologically active compounds. The scale of the Es(AMD) constant was put as close as possible to that of the Taft‐Kutter‐Hansch (TKH) Es parameter. For alkyl and halogen substituents, the Es(AMD) value was very close to the TKH Es value, but not for methoxy, isopropoxy, and such planar π‐bonded substituents as NO2 and Ph. Agrochemical and medicinal activities of various series of aromatic compounds taken from our earlier studies and the literature were analyzed quantitatively in terms of steric, electronic, and hydrophobic parameters, and the correlation equations formulated with Es(AMD) and Es for the steric effect of substituents, mostly those at ortho positions to the functional group, were compared. For several series of compounds, the Es(AMD) value gave better results than the TKH Es.
Quantitative Structure‐Property Relationships for the Polarizability, Solvatochromic Parameters and Lipophilicity
Authors: Schüürmann Gerrit 
Published: October 2006

AbstractThe polarizability αvol, the solvatochromic parameters π* and β and the lipophilicity as expressed by log Kow are subjected to regression analyses using calculated molecular parameters within the MNDO scheme. The resulting linear one‐ and more‐variable regression equations enable rapid approximate calculations for αvol, π* and β and log Kow of untested compounds; in particular, αvol is split into a molecular size and an electronic part which offers new possibilities for applications in quantitative structure‐activity relationships.
An Application of Unsupervised Neural Network Methodology Kohonen Topology‐Preserving Mapping to QSAR Analysis
Authors: Rose Valerie S. , Croall Ian F. , Macfie Halliday J. H. 
Published: October 2006

AbstractThe concept and methodology of artificial neural networks is introduced. Like pattern recognition, the techniques can be classified as supervised (requiring a priori knowledge of class membership) and unsupervised (making no assumptions about class membership). An unsupervised neural network method, Kohonen Topology‐Preserving Mapping, is applied to a wide matrix of physicochemical property data for a set of antifilarial antimycin analogues containing structural outliers. Principal component analysis failed to give a good 2D representation of the data set as a whole due to linear constraints in the model which gave undue influence to the outliers. Kohonen mapping compared favourably with non‐linear unsupervised statistical pattern recognition methods for 2D representation of compound similarity and for classification based on antifilarial activity. It may prove a valuable technique for QSAR in situations where a linear method does not model the data well and a high throughput of test compounds is indicated.
MULTICASE 1. A Hierarchical Computer Automated Structure Evaluation Program
Authors: Klopman Gilles 
Published: October 2006

AbstractA new algorithm is presented to analyze the structural features relevant to the biological activity of a set of molecules. The program called MULTICASE can, as its predecessor CASE (Computed Automated Structure Evaluator), automatically identify molecular sub‐structures that have a high probability of being relevant or responsible for the observed biological activity of a learning set comprised of a mix of active and inactive molecules of diverse composition. New, untested molecules can then be submitted to the program, and an expert prediction of the potential activity of the new molecule is obtained. MULTICASE differs from CASE in a great many ways, but the major algorithmic difference is the use of Hierarchy in the selection of descriptors, leading to the concept of Biophores and Modulators.
β‐Adrenoceptor Ligands: Characterization and Quantification of Drug Effects
Authors: Lemoine Horst 
Published: October 2006

AbstractSeveral methods based on receptor theory are introduced which are useful to characterize βAR in functional and biochemical experiments. βAR subtypes, β1AR and β2AR, which coexist in most organs of mammals including man, can be characterized in intact tissues analyzing the concentration‐dependent blockade of agonist‐induced effects by subtype‐selective antagonists. Non‐linear regression analyses allow the estimation of dissociation constants for antagonists and of fractional stimuli of agonists from which functional subtype‐selectivities can be deduced. A comparison of dissociation constants assessed by functional methods and by radioligand binding revealed an affinity loss of β1AR‐selective antagonists in plasmalemmal membranes. The analysis of binding of β2AR‐selective agonists, which are used for pharmacotherapy of bronchial asthma, in the absence and presence of GTP revealed characteristic differences in affinity for high and low affinity states of β2AR which correlate to different IA of agonists in stimulation of adenylate cyclase and of smooth muscle relaxation. A new agonist‐radioligand, 3H‐formoterol, is introduced which allows the measurement of binding kinetics. The slow dissociation of 3H‐formoterol may underlie the long‐lasting action of formoterol as assessed in its therapeutical use.
Comparison of Electrotopological State Indexes with Molecular Orbital Parameters: Inhibition of MAO by Hydrazides
Authors: Hall Lowell H. , Mohney Brian K. , Kier Lemont B. 
Published: October 2006

AbstractQSAR models for inhibition of monoamine oxidase (MAO) by aryloxyacetohydrazide derivatives were developed for a series of MO parameters computed with the AM1 Hamiltonian. These models were compared to those based on the recently developed electrotopological state index for. skeletal atoms. The structure interpretation is the same for both types of models: the NH group adjacent to the carbonyl group together with the carbon atom, gamma to the NH group, in the hydrocarbon substituent, account for more than 90% of the computed activity. However, the model based on E‐state indexes (r2 = 0.9012) is significantly superior to the one based on MO parameters (r2 = 0.7985); the standard deviation for the MO based model (s = 0.27) is 50% larger than that from the E‐state based model (r = 0.19). Several points of comparison between the models are presented. This study supports the idea that the electrotopological state is a useful representation of molecular structure information.
On Identifying Likely Determinants of Biological Activity in High Dimensional QSAR Problems
Authors: McFarland James W. , Gans Daniel J. 
Published: October 2006

AbstractA new approach to identifying descriptors associated with biological activity in ‘asymmetric’ data sets has been developed for high dimensional QSAR problems. As an example we have applied this approach to a problem first described by Selwood et al. [3]. Using Cluster Significance Analysis (CSA) in an explicit predetermined sequence of steps, we identified six likely determinants of antifilarial activity among antimycin analogs characterized by 53 descriptors. These determinants were ATCH5, ATCH2, VDWVOL, S8_1DX, ATCH4 and DIPV_X. Of them, only ATCH5, ATCH4 and DIPV_X were significant (R = 0.83) in a stepwise multiple regression analysis (MRA). These results are compared with those of the original workers and others who analyzed the data by different methods. By combining these descriptors with those identified by the other groups, we discovered a still better correlation. Jointly, ATCH5, ATCH4, DIPV_X, LOGP and MOFI_Y correlate highly with antifilarial potency (R = 0.91). The problem of discovering the ‘true’ determinants of biological activity in high dimensional asymmetric data sets is discussed.
Modelling the Toxicity of Organophosphates: a Comparison of the Multiple Linear Regression and PLS Regression Methods
Authors: Verhaar Henk J. M. , Eriksson Lennart , Sjöström Michael , Schüürmann Gerrit , Seinen Willem , Hermens Joop L. M. 
Published: October 2006

AbstractA set of nine biological endpoints, comprising data for bioconcentration, biotransformation, AChE inhibition and acute aquatic toxicity, for a set of twelve organophosphorothionates was modelled using a set of ten non‐empirical, mainly quantum‐chemical, descriptors, employing two different techniques, viz. Multiple Linear Regression and Partial Least Squares projection to latent variables regression.For these compounds and biological endpoints, PLS models are not only quantitatively better than MLR models, as judged by model fit (r2) and ‘predictivity’ (PRESS/SSY), but it is also shown that there exist ways of mechanistically interpreting the results of the PLS models. These interpretations can be used to come to a better understanding of the processes involved in organophosphorothionate toxicity and to generate even better, more mechanistically based models. This finding clearly refutes the commonly held belief that PLS models are inherently more difficult to interpret than comparable MLR models.
Theoretical Study on the Metabolism of Caffeine by Cytochrome P‐450 1A2 and its Inhibition
Authors: Sanz Ferran , López‐de‐Briñas Elena , Rodríguez Jesüs , Manaut Francesc 
Published: October 2006

AbstractThe primary metabolism of caffeine (1,3,7‐trimethylxanthine) is catalyzed by the isozyme P‐450 1A2 which has toxicological relevance because it is involved in the activation of some chemicals to carcinogenic compounds. A theoretical model for the demethylation of caffeine is proposed by means of the study of the molecular electrostatic potential (MEP) distributions of caffeine and other xanthine derivatives that are inhibitors of this metabolic process. Negative zones of these distributions show a common triangular pattern in the xanthine plane. The model proposes that the alignment of the caffeine molecule in the active site is determined by these negative MEP zones. An interesting finding was that all the methyl groups to be removed have at least a MEP minimum at a distance of approximately 3 Å. This feature would explain the preference for the N3 demethylation leading to paraxanthine (1,7‐dimethylxanthine) because only this methyl group is placed at a distance of 3 Å from the deepest MEP minimum. Another experimental observation consistent with the proposed model is the inhibition of caffeine demethylation by several 8‐methylxanthines. Among them, 1,3,8‐trimethylxanthine, furafylline (1,8‐dimethyl‐3‐(2‐furfuryl)xanthine) and 1,8‐dimethyl‐3‐phenylxanthine were considered in the present study. The inhibition is explained by the fact that all these compounds have a methyl on C8 placed at a distance of 3 Å from the deepest MEP minimum.
Variable Selection in QSAR Studies. I. An Evolutionary Algorithm
Authors: Kubiny Hxugo 
Published: October 2006

AbstractIn QSAR studies of large data sets, variable selection and model building is a difficult, time‐consuming and ambiguous procedure. While most often stepwise regression procedures are applied for this purpose, other strategies, like neural networks, cluster significance analysis or genetic algorithms have been used. A simple and efficient evolutionary strategy, including iterative mutation and selection, but avoiding crossover of regression models, is described in this work. The MUSEUM (Mutation and Selection Uncover Models) algorithm starts from a model containing any number of randomly chosen variables. Random mutation, first by addition or elimination of only one or very few variables, afterwards by simultaneous random additions, eliminations and/or exchanges of several variables at a time, leads to new models which are evaluated by an appropriate fitness function. In contrast to common genetic algorithm procedures, only the “fittest” model is stored and used for further mutation and selection, leading to better and better models. In the last steps of mutation, all variables inside the model are eliminated and all variables outside the model are added, one by one, to control whether this systematic strategy detects any mutation which still improves the model. After every generation of a better model, a new random mutation procedure starts from this model. In the very last step, variables not significant at the 95% level are eliminated, starting with the least significant variable. In this manner, “stable” models are produced, containing only significant variables. A comparison of the results for the Selwood data set (n = 31 compounds, k = 53 variables) with those obtained by other groups shows that more relevant models are derived by the evolutionary approach than by other methods.
Molecular Similarity Determination of Heteroaromatics Using CoMFA and Multivariate Data Analysis
Authors: Langer Thierry 
Published: October 2006

AbstractThe molecular similarity concept serves as a tool for rationalizing the design of potential bioactive molecules. This report examines a way to determine molecular similarity among heteroaromatic moieties by calculating new QSAR descriptors using the CoMFA approach. The descriptors for heteroaromatic substituents in organic molecules derived in this study permit to take into account differences in anchoring positions of such substructures in a given molecule. The aromatic moieties 1‐37 have been characterized by their interaction energies calculated using the CoMFA method. Principal component analysis of the interaction energy matrices was performed in order to derive new ‘principal properties’ of the heteroaromatics. A partitioning of the heteroaromatic substituents into families has been done both by hierarchical clustering of the obtained principal components and by applying a factorial design method. These procedures allow a classification of structures according to their molecular similarity.