bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypotensive action of syringin from Syringa vulgaris
Authors: Ahmad Mansoor , Aftab Khalid 
Published: October 2006

AbstractNaturally occurring syringin was isolated from the bark of Syringa vulgaris (Oleaceae), and its pharmacological action examined on anaesthetized Wistar rats. When the drug was introduced intravenously, it caused a dose dependent fall in systolic, diastolic and mean arterial blood pressure, whereas heart rate also decreased at a slightly higher dose. The hypotensive activity was not inhibited by antihistamine or antimuscarinic agents. Syringin has no effect on the pressor effect induced by norepinephrine or carotid occlusion.
Pharmacological screening of the methanol and dichloromethanol extracts of Genista patens
Authors: Bello R. , Barrachina M. D. , Martínez‐Cuesta M. A. , Esplugues J. , Yúfera E. Primo 
Published: October 2006

AbstractThe pharmacological effects of the dichloromethanol and methanol extracts obtained from leaves and stems of Genista patens DC were analysed in in vitro and in vivo models. Both extracts showed low acute toxicity (LD50 > 3 g/kg), CNS depressor and antiinflammatory activity, and similar analgesic effect in models of chemical and thermal stimulation. Furthermore, the dichloromethanol extract (1–20 mg/kg) induced a pronounced dose‐dependent decrease on blood pressure. On isolated organs, the dichloromethanol extract (1, 10, 100 μg/mL) shifted the concentration‐effect curve to the right for ACh and reduced the Emax induced by histamine without modifying responses induced by noradrenaline and serotonin.
Activity of Osyris quadripartita salzm. Methanol extract on capillary permeability in rats
Authors: Gómez M. E. , Ayuso M. J. , Toro M. V. 
Published: October 2006

AbstractA methanol extract of Osyris quadripartita Salzm., with high content of flavonoids was found to be effective in reducing the increased capillary permeability induced in rats by various chemical mediators involved in the inflammatory process, namely histamine (HA), 5‐hydroxy‐triptamine (5‐HT) and bradykinin (BK). Pretreatment with the MeOH extract (250 mg/kg i.p.) afforded significant protection against the increase in capillary permeability induced by HA (% protection = 96.6), 5‐HT (% protection = 53.8) and BK (% protection = 87.9).
Modulatory effects of Artemisia annua extracts on human complement, neutrophil oxidative burst and proliferation of T lymphocytes
Authors: Kroes B. H. , van Ufford H. C. Quarles , Boer R. L. Tinbergen‐de , van den Berg A. J. J. , Beukelman C. J. , Labadie R. P. , van Dijk H. 
Published: October 2006

AbstractAir‐dried aerial parts of Artemisia annua were extracted with petroleum ether, diethyl ether, ethyl acetate, ethanol and water successively. The extracts were screened for their in vitro effects on human complement, proliferation of T lymphocytes, and chemiluminescence by zymosan‐stimulated polymorphonuclear leukocytes. All extracts exhibited dose‐dependent inhibitory activities in our immunoassays. The highest activity towards the classical pathway of complement was found in ethyl acetate and ethanol extracts, whereas in the chemiluminescence assay, diethyl ether and ethyl acetate extracts showed the most pronounced inhibitory activities. In the T‐cell proliferation assay, the diethyl ether extract exhibited the most potent inhibitory effect. Artemisinin showed no immunomodulatory activity in our assays.
13C‐NMR and 1H‐NMR Chemical Shifts in a Correlation Analysis of Benzotriazole Derivatives Active as Plant Growth Regulators
Authors: Sparatore F. , Caliendo G. , La Rotonda M. I. , Novellino E. , Silipo C. , Vittoria A. 
Published: October 2006

AbstractFollowing preliminary observations on auxin‐like activity of several 1‐ and 2‐substituted benzotriazole isomers, a few new derivatives have been synthesized and tested. In attempting to quantify by QSAR the structural properties of a large set of compounds and with the aim to rationalize the structure‐activity relationships taken into account in a previous study by a set of indicator variables, attention was turned to the analysis of 13C‐NMR and 1H‐NMR chemical shifts relative to the substituent carbon atom attached on the nitrogen of the benzotriazole ring. The 13C‐NMR chemical shift can be useful as an independent parameter in QSAR. Considerations of the general applicability of sigma inductive constants for predicting physicochemical properties of complex heteroaromatic systems such as those under study are discussed. Finally it is shown that there are important electronic and steric components which play a major role in promoting the auxin‐like activity of compounds under examination.
Modeling the Interaction of Small Organic Molecules with Biomacromolecules (the Oasis Approach). V. Toxicity of Phenols to Algae “Lemna Minor”
Authors: Mekenyan Ovanes G. , Bonchev Danail G. , Enchev Venelin G. 
Published: October 2006

AbstractThe recently developed OASIS approach See Refs. 1 to 4 for Parts I to IV of this series, as well as Refs. 6 and 7 for a detailed description of the approach.
is applied to the modeling of substituted phenol toxicity. The best models derived show a certain contribution of the electronic factor in addition to the hydrophobicity factor; while the phenol geometric properties were found to be insignificant. The superdelocalizability indices characterizing the electron acceptor properties of the oxygen and its neighbouring carbon atom were found to be of importance along with the phenol acidity used in previous models and they can replace the latter in calculating substituted phenol toxicities. The complicated mechanism of the toxic agent‐receptor interaction is thus supposed to include some charge transfer from the biosubstrate to these two phenolic atoms with possible formation of a covalent or a hydrogen bond, although the charge‐controlled reactions seem to prevail.
Calculation of Molecular Volumes from Molecular Fragments via Valence Electron Indices
Authors: Govers Harrie , De Voogt Pim 
Published: October 2006

AbstractIt is shown that van der Waals volumes of 1‐atomic fragments, c.q. hydrides, can be predicted accurately via indices denoting the number of non‐hydrogen valence electrons. The introduction of a principal quantum number dependence of orbital volumes turned out to be necessary, which led to a modified molecular connectivity model. From these fragmental indices molecular valence electron indices were derived, which are demonstrated to be accurate predictors of the molecular volume of polycyclic aromatic compounds in an additive model.
Substructural Analysis of Antineoplastic Compounds in Respect of in Vivo Tumor Models
Authors: Pajeva Ilza , Golovinsky Evgeny 
Published: October 2006

AbstractA substructural analysis of antineoplastic compounds is provided with respect to two in vivo tumor models: lymphoid leukemia L1210 (L1210) and Lewis lung carcinoma (LL). The activity data are expressed by 4 levels of activity against L1210 and LL. The structures of the compounds are described by means of structural features derived from a structure‐activity relationship (SAR) oriented language for two‐dimensional chemical structure representation. A statistical‐heuristic technique is applied to obtain, for each structural feature, a weight for each activity level. On the basis of the weights, the contributions of the structural features to the probabilities of activity against L1210 and LL models are estimated. The features contributing to the relevant probabilities to the greatest extent are located and analyzed from a biochemical point of view. The results obtained show the suitability of the features for compounds' activity recognition and identification of substructures significant for the investigated activities.
QSAR Analysis in 2,4‐Diamino‐6,7‐dimethoxy Quinoline Derivatives – α1‐Adrenoceptor Antagonists – Using the Partial Least Squares (PLS) Method and Theoretical Molecular Descriptors
Authors: Cocchi Marina , Menziani M. Cristina , Rastelli Giulio , de Benedetti Pier G. 
Published: October 2006

AbstractTheoretical molecular descriptors were derived for fifteen 2,4‐diamino‐6,7‐dimethoxy quinoline derivatives α1‐adrenoceptor antagonists both from molecular orbital indices (AM1) and modelling of molecular shape (QUANTA 2.1.A). Quantitative structure‐activity relationships (QSAR) were obtained between the theoretical descriptors and the α1‐binding affinities (from literature) by using the Partial Least squares (PLS) method. The QSAR model obtained is satisfying both from a predictive and interpretative point of view and clearly depicts the role of the protonated quinoline nucleus at the α1‐adrenoceptor. In fact, the more electrophilic the N1‐H (+) group, the higher the α1‐binding affinity. Furthermore, it suggests that hydrophobicity is a second key feature for an effective receptor interaction.
The Reactivity of 2‐(4‐Phenylsubstituted)‐α,β‐Unsaturated Carboxylic Acids with Diazodiphenylmethane
Authors: Ušćaumlića Gordana S. , Krstića Vera V. , Muškatirovića Milan D. 
Published: October 2006

AbstractIn connection with a study of the transmission of polar effects through ring double bonds, double bonds in open chain systems and delocalized double bonds, the reactivity of 2‐(4‐phenylsubstituted)‐α,β‐unsaturated carboxylic acids with diazodiphenylmethane in ethanol was investigated. The rate data for 2‐(4‐phenylsubstituted)‐cyclohex‐1‐ene carboxylic acids, 2‐(4‐phenylsubstituted)‐benzene carboxylic acids, cis‐3‐and 4‐substituted and trans‐3‐ and 4‐substituted cinnamic acids were correlated with a simple Hammett equation by means of the σp and σm constants and with an extended Hammett equation to detect the presence or absence of steric effects as well as the composition of the electrical effect. The transmission of polar effects through the different double bonds was discussed in terms of the polar susceptibility constant δ and steric interaction of the phenyl and carboxylic group.
Inhibition of Thermolysin and Bacillus brevis Neutral Proteinase by Organic Solvents and Some Related Compounds
Authors: Paberit Nadezhda , Paberit Mart 
Published: October 2006

AbstractInhibition of thermolysin and Bacillus brevis neutral proteinase (NP) reactions with N‐(3‐(2′‐furyl)acryloyl)glycyl‐L‐leucinamide by organic solvents and some other simple organic compounds (alkanols, aromatic compounds etc., in total 33 substances) was studied. The enzymes showed very similar affinities for the inhibitors in the whole range of Ki variation (3.7 orders of magnitude). A linear dependence with a nearly unitary slope between the pKi values and log P's of the compounds was found. The inhibitory power of the compounds, whose molecules are longer than those of propanol or benzene, depended on their ability to donate a hydrogen bond. pKi's of the compounds, in which substituents attached to the propyl group or benzene ring are unable to donate the hydrogen bond, fell off the correlation line; the deviation was proportional to the van der Waals volume of the substituent. pKi's of tert‐butanol and cyclohexanol also fell off the correlation line. Geometrical thickness of their molecules exceeds that of the other studied inhibitors; this may explain their lowered affinity for the enzymes. 6,6‐ or 7,5‐bicyclic compounds did not inhibit these enzymes.
Application of Functional‐Link Net in QSAR. 1. QSAR for Activity Data Given by Continuous Variate
Authors: Liu Qian , Hirono Shuichi , Moriguchi Ikuo 
Published: October 2006

AbstractWe attempted to apply a new pattern recognition method called “functional‐link net” (Klassen and Pao, 1988) to QSAR. In contrast to the linear weighting produced by the generalized delta rule net often used in neural nets, the functional‐link net acts on a pattern element (a structural parameter in QSAR) or on the entire pattern itself to generate a set of nonlinear functions. In usual QSAR studies, linear forms of parameters are generally used. But, in many cases, parameters might contribute semilinearly to activity. Such a semilinear contribution of parameters can be examined by semilinearly transforming the parameters into a new parameter vector using a procedure with the architecture of the functional‐link net. The new method presented here was devised for analysis of QSAR from activity data given by a continuous variate. The application of this method to QSAR of several data sets of carboquon analogues with antileukemic activity gave better results than those given by multiple regression analysis of the same data sets. The comparison of the results with those given by the generalized delta rule net also showed that FUNCLINK was superior in the predictive ability.
A Study on pK and Partition Coefficient of Substituted Benzoic Acids in SDS Anionic Micellar System
Authors: Garrone Adele , Marengo Emilio , Fornatto Elisa , Gasco Alberto 
Published: October 2006

AbstractApparent ionization constants (pK) of a series of m‐ and p‐ substituted benzoic acids were measured by potentiometric titrations in an anionic micellar system (SDS, Sodium Dodecyl Sulphate). From these data, the binding constant K and the partition coefficient between micellar and aqueous pseudophases Pmic, were estimated for each derivative. Collander type regressions between log Pmic and log Poct are discussed. pK values correlate well with a linear combination of σ, πoct and MR molecular descriptors.
Routes to Histamine H2‐Agonists
Authors: Timmerman Hendrik 
Published: October 2006

AbstractIn this paper the design, synthesis and primary biological testing of several new H2‐agonists are presented. The existing agonists dimaprit and impromidine have been used as starting points.Dimaprit seems to be the only member of its class which is an H2‐agonist; close analogues of dimaprit proved to be inactive as H2‐agonists.In impromidine the moieties constituting the molecule are considered to play different roles: the unsubstituted imidazole is required for receptor activation, whereas the guanidino and the methyl‐substituted imidazole are needed for additional receptor binding. Based on this concept several new and potent impromidine‐like H2‐agonists were obtained.Using the fastidious nature of dimaprit for H2‐agonism, computational approaches lead to the design of 2‐aminothiazoles as H2‐agonists. Several new H2‐agonists, also of the impromidine‐type, were obtained. This class of compounds provides not only potent, but also selective (negligible effects on H1‐ and H3‐receptors) H2‐agonists.
Industrial Drug Research: Development of Ca‐Antagonistic Vasodilators
Authors: Edgar Boo 
Published: October 2006

AbstractThe prime aim of industrial drug research is the development of new therapeutics; correspondingly it has to consider not only drug‐receptor interaction, but also such important aspects as pharmacokinetics, side effects and toxicology. An example for this complex pattern of industrial drug research is given here for the development of the dihydropyridine‐like Ca‐antagonist felodipine. Several felodipine analogues with different ester groups in 3‐ and 5‐position of the dihydropyridine ring were synthesized and their biological activities evaluated in screening procedures. Both in vitro and in vivo potency was determined, as well as selectivity for vascular smooth muscle, in comparison to cardiac muscle. Structure‐activity relationships were studied in a group of these dihydropyridine esters (DHP‐esters) to ensure that the compound selected for further biological evaluation (felodipine) is close to the optimum as far as the screening parameters are concerned.In the second part of the paper pharmacokinetic properties and clinical profile of felodipine are summarized.
Amino Acids Characterization by GRID and Multivariate Data Analysis
Authors: Cocchi Marina , Johansson Erik 
Published: October 2006

AbstractThe twenty coded amino acids have been characterized by their interaction energies, calculated by the program GRID, with six different probes mimicking various functional groups which can be involved in peptide‐peptide interactions. Principal Component Analysis (PCA) have been used to derive amino acids principal properties and comparing the amino acids classification obtained with the one derived by the previous published amino acids z‐scales. Partial Least Squares (PLS) method has been used to test the performance of GRID probe interaction energies and the newly derived principal properties in peptide's QSAR modeling. A better separation of amino acids according to the electronic features of the side chain is obtained. The inhibitory activity of the set of peptides considered has been satisfactorally modelled.
“Classical” and “Magnetic” Aromaticities as new Descriptors for Heteroaromatics in QSAR. Part 3 [1]. Principal Properties for Heteroaromatics
Authors: Caruso Loredana , Musumarra Giuseppe , Katritzky Alan R. 
Published: October 2006

AbstractA set of twentyfour monocyclic and benzo‐fused heteroaromatics were multivariately characterized by five experimental aromaticity descriptors: one geometric, two energetic and two magnetic aromaticity scales. Two principal properties (PP), designated as “classical” and “magnetic” respectively, were calculated from the 5 × 24 data set, by a two principal components (PC) model explaining 79.5% of variance. The first PP was shown to be related to I'x aromaticity scale, available for a wider set of heteroaromatics. The above PPs, together with other descriptors accounting for the position of attachment of the ring, may be used in developing strategies for selecting heteroaromatic moieties in experimental design aimed at the optimization of structures for pharmaceutical or toxicological testing.
On the Reliability of Calculated Log P‐values: Rekker, Hansch/Leo and Suzuki Approach
Authors: Rekker R. F. , Laak A. M. Ter , Mannhold R. 
Published: October 2006

AbstractA number of fragmental approaches for calculation of drug lipophilicity (log P) have been developed in recent years.Among these the procedures of Rekker, Hansch and Leo and that of Suzuki and Kudo offer good possibilities for setting up computerized versions of log‐P calculation. This paper presents a comparative overview of the results of these three approaches for two series of hydrocarbon structures as well as for 36 selected drugs as tabulated by Rekker and Mannhold in their monograph “Calculation of Drug Lipophilicity”.The presented data demonstrate quite clearly that in a number of cases unexpected and unacceptable artefacts show up. Our final conclusion is that – at least for the series we chose for demonstration – the ultimate goal for faultless log P‐calculations, although within reach, has not yet been fully realized.
Comparison of QSAR and Molecular Similarity Approaches for a Structure‐Activity Relationship Study of DHFR Inhibitors. DHFR Inhibitors: QSAR and Molecular Similarity Approaches
Authors: Stanton David T. , Murray Wallace J. , Jurs Peter C. 
Published: October 2006

AbstractA comparison is made between classical QSAR approaches using multivariate linear regression analysis and molecular similarity analysis (MSA) using inhibitors of dihydrofolate reductase (DHFR). A wide variety of descriptors derived directly from molecular structure are examined with both QSAR and MSA approaches. Three separate measures of molecular similarity are examined to determine how each compares with the QSAR method in the context of the descriptors used. The QSAR method yielded a model with a R2 = 0.927 whose descriptors indicate that molecular size, shape and hydrogen bonding acceptor groups are important to activity. Molecular similarity approaches did not provide as good a model. The best correlation between pKi values and any given similarity metric was obtained with the Tanimoto coefficient.
Relationship Between the Lipophilicity and Specific Hydrophobic Surface Area of Non Homologous Series of Nonionic Surfactants
Authors: Forgács Esther , Cserháti Tibor 
Published: October 2006

AbstractThe lipophilicity (RM), specific hydrophobic surface area and the relative strength of interaction between trimethyl‐β‐cyclodextrin and 39 nonionic surfactants having different hydrophobic moieties has been determined by charge‐transfer thin‐layer chromatography using methanol as an organic modifier. RM values decreased linearly with increasing concentration of methanol. The significant correlation between the RM value extrapolated to water and the specific hydrophobic surface area indicates that these surfactants can be considered from the chromatographic point of view as a homologous series of solutes independently of their structural inhomogeneity. Stepwise regression analysis suggested that the length of alkyl chain in the hydrophobic moiety, the presence of sorbite and phenyl group in the surfactant molecule, and the number of ethyleneoxide groups per molecule have the highest impact on their hydrophobic parameters. The relative strength of surfactant‐cyclodextrin interaction significantly depended on the lipophilicity of the surfactants, and on the presence of phenyl group and ester bonds in the surfactant molecule.
A Three‐Dimensional Technique for the Calculation of Octanol‐Water Partition Coefficients
Authors: Waller Chris L. 
Published: October 2006

AbstractOctanol‐water partition coefficients, as logPs, are frequently used to describe transportability and membrane permeability of chemical compounds. Because of this they represent an integral part of quantitative structure‐activity relationship (QSAR) theory. Since the analytical determination of logPs is a tedious process, many empirical techniques for their calculation have been developed. The additive fragment‐based technique, clogP, represents the most highly validated algorithm designed for this purpose. However, it has been observed that clogP is incapable of distinguishing between structural isomers in a congeneric series of compounds. This is primarily a result of the lack of necessary “factors” for the characterization of the substituent effects. As an alternative to additional parameterization of the clogP methodology, a novel technique for the calculation of octanol‐water partition coefficients based on three‐dimensional descriptors was developed which is capable of accurately predicting the experimentally‐determined logPs for a congeneric series of structural isomers.
Theoretical Descriptors of Nucleic Acid Bases. Application to DNA Promoter Sequences
Authors: Norinder Ulf , Jonsson Jörgen 
Published: October 2006

AbstractTheoretical descriptors for nucleic acids are generated by applying principal component analysis to 3‐D field data of non‐bonded and charge‐charge interaction type. These descriptors are subsequently used to develop quantitative sequence‐property models with good predictability for E. coli transcriptional DNA‐promoter sequences using the method of partial least squares projections to latent structures (PLS). The resulting 3‐D contour maps can be used to investigate requirements for new nucleic acids to be synthesized in order to obtain sequences with altered activities.
Theoretical Investigations on Antimuscarinic Ethylthio and Ethoxy Derivatives of Adiphenine and 4‐DAMP
Authors: Romanelli M. Novella , Höltje Hans‐Dieter , Scapecchi Serena 
Published: October 2006

AbstractThe unexpected differences in biological activity of some sulfurated muscarinic antagonists, compared to their oxygenated analogues, is explained using theoretical methods based on molecular mechanics and molecular orbital calculations. Interaction energies calculated for both types of ligands with a receptor model (M1) show that binding is more favourable for the sulfurated than the oxygenated molecules. This can be explained with the different geometrical and electronical properties (but not conformational) of the molecules.