bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of compounds of plant origin on the mutagenicity and metabolism of the tobacco‐specific nitrosamine NNK
Authors: Miller C. H. , Hamilton S. M. , Teel R. W. 
Published: October 2006

AbstractWe have investigated the effects of five phytochemicals on the microsomal‐dependent mutagenicity and metabolism of the tobacco‐specific nitrosamine, 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK). Two compounds, d‐limonene and silymarin, had no effect on NNK‐induced mutagenesis in Salmonella typhimurium TA1535 over the concentration range of 0.1–0.4 μmol/plate. Diallyl sulphide was weakly antimutagenic at a concentration of 0.4 μmol/plate. Both capsaicin and tannic acid showed a dose‐dependent inhibition of mutagenesis in TA1535. Metabolism studies using [3H]NNK indicated that the effects of the phytochemicals on NNK‐induced mutagenesis did not always correlate with the effects on NNK metabolism. α‐Carbon hydroxylation reactions are considered the most significant pathways involved in the metabolic activation of NNK to mutagenic and carcinogenic species. D‐Limonene and silymarin (0,4 μmol) had the least inhibitory effect on the total α‐carbon hydroxylation reactions, 19% and 28%. Capsaicin and diallyl sulphide inhibited these pathways by 74% and 70%. Tannic acid, the most potent phytochemical tested in this study, inhibited total α‐carbon hydroxylation pathways by 99%.
Inhibitory activity of extracts of Alternanthera brasiliana (amaranthaceae) against the herpes simplex virus
Authors: Lagrota M. H. C. , Wigg M. D. , Santos M. M. G. , Miranda M. M. F. S. , Camara F. P. , Couceiro J. N. S. S. , Costa S. S. 
Published: October 2006

AbstractFive extracts from A. brasiliana, obtained through different procedures, showed anti‐HSV activity. The best activity was detected in a fraction (B) that was obtained from the crude cold aqueous extract on Sephadex G15. Fraction B showed low cellular toxicity and inhibition from 32.4% to 99.9% at concentrations from 6.2 to 50.0 μg/mL, exhibiting a therapeutic index of 32. Fractions obtained on Sephadex G100 and reversed‐phase column also showed considerable inhibition. Fraction B did not show any virucidal activity, however, its inhibitory activity was revealed during the later stages of the virus replication cycle. This fraction showed activity on DNA synthesis of infected cells.
Antiurolithiatic activity of lupeol, the active constituent isolated from Crateva nurvala
Authors: Anand R. , Patnaik G. K. , Kulshreshtha D. K. , Dhawan B. N. 
Published: October 2006

AbstractIn the traditional Indian system of medicine Crateva nurvala (Hindi: Varuna) constitutes a major ingredient of formulations used to treat urinary disorders including urolithiasis. In an earlier study we confirmed the antiurolithiatic activity in the crude extract of the plant, and further fractionation led to the isolation of the active constituent lupeol (Lup‐20(29)‐en‐3β‐ol). Antiurolithiatic activity of lupeol was assessed in rats by observing the weight of the stone, biochemical analysis of serum and urine, and histopathology of bladder and kidney. Lupeol not only prevented the formation of vesical calculi but also reduced the size of the preformed stones.
Antiprotozoal activities of Centipeda minima
Authors: Yu H. W. , Wright C. W. , Cai Y. , Yang S. L. , Phillipson J. D. , Kirby G. C. , Warhurst D. C. 
Published: October 2006

AbstractIn vitro activity against Giardia intestinalis was used for bioassay‐guided fractionation of crude extracts from C. minima. The sesquiterpene lactone, brevilin A was isolated and found to have antigiardial activity (IC50 = 16.1 μM) and was similarly active in vitro against Entamoeba histolytica (IC50 between 4.5 and 9 μM) and against Plasmodium falciparum (IC50 = 9.42 μM). Three flavonoids, quercetin, quercetin 3‐methyl ether and kaempferol 7‐glucosylrhamnoside were also isolated.
Effects of glycowithanolides from Withania somnifera on morphine‐induced inhibition of intestinal motility and tolerance to analgesia in mice
Authors: Ramarao P. , Rao K. T. , Srivastava R. S. , Ghosal S. 
Published: October 2006

AbstractEffects of glycowithanolides (Ws, 10–150 mg/kg, i.p.), consisting of sitoindosides VII‐X, in combination with withaferin‐A, from Withania somnifera, in Swiss mice were evaluated on (i) morphine‐induced inhibition of gastrointestinal tract (GIT) transit and (ii) development of tolerance to morphine‐induced analgesia. Pretreatment with Ws significantly reversed the morphine (5 mg/kg, s.c.)‐induced inhibition of GIT transit at all doses. Ws (100 mg/kg, i.p., o.d., for 10 days) significantly inhibited the development of tolerance to morphine‐induced analgesia. Ws per se did not influence the intestinal motility nor did it produce any perceptible analgesic effect. The present and earlier findings with Ws suggest its potential in alleviating the adverse effects of morphine and the attendant immunodepression.
In vitro antimycotic activity of some natural products against Saprolegnia ferax
Authors: Perrucci S. , Cecchini S. , Pretti C. , Cognetti A. M. Varriale , Macchioni G. , Flamini G. , Cioni P. L. 
Published: October 2006

AbstractDuring the in vitro screening of four essential oils and six substances of vegetable origin against the test fungi Saprolegnia ferax, thyme and savory essential oils, carvacrol and thymol exhibited the best antifungal activity at the lower concentrations. The antimycotic activity of malachite green, formalin and sodium chloride was also tested.
Spasmolytic action of the essential oil of Achillea ageratum L. in rats
Authors: de la Puerta R. , Herrera M. D. 
Published: October 2006

AbstractThe spasmolytic activity of Achillea ageratum L. essential oil in isolated rat duodenum has been in estigated. The essential oil was found to present a marked spasmolytic activity against acetylcholine and BaCl2 via a non‐competitive type of antagonism.
Antitumour potential of pollen extract on lewis lung carcinoma implanted intraperitoneally in syngeneic mice
Authors: Furusawa E. , Chou S. C. , Hirazumi A. , Melera A. 
Published: October 2006

AbstractA defined pollen extract of selected plants has been reported to possess some pharmacological activities on chronic prostatis or benign prostatic hyperplasia. This paper describes the antitumour potential of the water soluble fraction (Cernitin T60) of pollen extract against Lewis lung carcinoma implanted intraperitoneally in syngeneic mice. Cernitin T60 was not cytotoxic in cell cultures at concentrations up to 2.5 mg/mL, while it is significantly prolonged the life‐span of mice carrying the tumour without any apparent side effects at 0.5 g/kg. In addition, Cernitin T60 demonstrated beneficial therapeutic effects in an additive fashion on the life‐span of mice when it was combined with standard cytotoxic antitumour drugs such as adriamycin, cisplatin, vincristine, methotrexate, fluorouracil, or thioguanine. The antitumour potential of Cernitin T60 was completely abolished by treatment with inhibitors of macrophage functions (2‐chloroadenosine or carrageenan), but not with a T‐cell inhibitor (cyclosporin A). Cernitin T60 appears to be a potent immunostimulator of macrophages.
Effect of buckwheat extract on free radical generation in rabbits administered high‐fat diet
Authors: Wójcicki J. , Samochowiec L. , Gonet B. , Juźwiak S. , Dabrowska‐Zamojcin E. , Katdońska M. , Tustanowski S. 
Published: October 2006

AbstractIn this study the effect of buckwheat extract (BE) on the level of malondialdehyde (MDA), lipids and hormones, and on the concentration of ascorbate free radicals in the liver (compared with rutin) in animals receiving a highfat diet (HFD) was measured. Male mongrel rabbits were randomly divided Into four groups: (1) control, (2) animals given HFD containing cholesterol and coconut oil, (3) rabbits treated with HFD + BE, (4) HFD + rufin, over a period of 12 weeks. The concentration of MDA in rabbits of group 3 (HFD + BE) was slightly but significantly decreased, whilst the number of ascorbate free radicals, examined in vitro, in the liver was markedly elevated. The level of testosterone in rabbit blood serum (group 3) was increased, but the insulin concentration was significantly diminished (in comparison with group 2). The content of total cholesterol and triglyceride in the liver of animals maintained on BE was decreased. Quite distinct superiority of BE, compared with rutin, was shown.
Active constituents of the bulbs of Fritillaria ebeiensis and their antitumour activity in mice
Authors: Ping Li , Guojun Xu , Luoshan Xu , Yixian Wang 
Published: October 2006

AbstractThe crude alkaloid of Fritillaria ebeiensis G. D. Yu et G. Q. Ji, administrated orally at a given dose, showed strong antitumour activity in inhibiting the growth of the solid type of hepatoma in mice. Chemical studies revealed that the active principles in this crude drug were verticine, verticinone and ebeiedine obtained from this species for the first time. This paper deals with the isolation and activity of these principles.
Acteoside: A new antihypertensive drug
Authors: Ahmad Mansoor , Rizwani Ghazala H. , Aftab Khalid , Ahmad Viqar Uddin , Gilani Anwarul Hasan , Ahmad Shahida Perveen 
Published: October 2006

AbstractActeoside is a phenylpropanoid, reported as a chemical constituent from different plant species, and was isolated as a pure compound on RP‐HPLC from the violet flowers of Syringa vulgaris. On pharmacological evaluation this compound exhibited a dose‐dependent decrease in sytolic, diastolic and mean arterial blood pressure in normotensive pentothal anaesthetized rats. The median effective dose was 10 mg/kg and lasted for 2–3 min, whilst heart rate also decreased.
Effects of an aqueous extract of Terminalia arjuna on isolated rat atria and thoracic aorta
Authors: Karamsetty Mallikharjuna , Ferrie Thomas J. , Kane K. A. , Gray A. I. 
Published: October 2006

AbstractTerminalia arjuna (Combretaceae) is used traditionally in ayurveda, to treat a variety of cardiovascular disorders. The aims of this study were to characterize the positive inotropic effect of the aqueous extract of T. arjuna bark in isolated paced rat left atria and to study its effects on a vascular smooth muscle preparation, the rat thoracic aorta. The crude and semipurified aqueous extracts produced a positive inotropic effect of rat atria and the maximum contraction was comparable to that produced by isoprenaline. The positive inotropic effect of the extract was completely blocked by a β‐adrenoceptor blocker, propranolol, and an uptake‐1 blocker, cocaine. In precontracted aorta, the aqueous extract produced a contraction followed by relaxation. Propranolol did not block the relaxant effect of the aqueous extract. It is concluded that the positive inotropic effect of the aqueous extract was mediated via an action on β1‐adrenoceptors and was likely to be due to the release of noradrenaline from the sympathetic nerve endings. The vasorelaxant effect of the extract, however, was not mediated via an action on β2 adrenoceptor.
Further antibacterial diterpenes from the bark and leaves of Juniperus procera hochst. ex Endl
Authors: Muhammad Ilias , Mossa Jaber S. , Al‐Yahya Mohammed A. , Ramadan Ahmed F. , El‐Feraly Farouk S. 
Published: October 2006

AbstractThe bark of Juniperus procera yielded three antibacterial diterpenoids, (+)‐E‐communic acid (1), (+)‐Z‐communic acid (2) and (+)‐totarol (3). Compound 2 exhibited significant activity against Gram‐positive bacteria, while 1 was found to be less active. Compound 3, on the other hand, demonstrated potent activity against Mycobacterium organisms, while its corresponding 3β‐hydroxy‐derivative 4 was found to be inactive. The chromatographic separation of (+)‐Z‐communic acid (2) from (+)‐E‐communic acid (1) and those previously unreported spectral data of 1 and 2 are described. In addition, the leaves yielded (+)‐8α‐acetoxyelemol, β‐peltatin A methyl ether and deoxypodophyllotoxin.
The Measurement of Partition Coefficients
Authors: Dearden John C. , Bresnen Gaynor M. 
Published: October 2006

AbstractPartition coefficient (P) is a widely‐measured property, yet there is considerable variation among published log P values. This paper examines the factors that can affect the measurement of partition coefficient, and makes recommendations as to good practice. Accuracy of partition coefficient determination can be affected by temperature, lack of mutual phase saturation, pH, buffer type and concentration, phase miscibility, solute concentration, solute and solvent purity, solute stability, phase volume ratio, solute adsorption and failure to reach equilibrium conditions. It is recommended that partitioning be carried out at constant temperature using either a stirred flask technique or the filter probe.
The Relationship Between Chemical Structure and the Logarithm of the Partition Coefficient
Authors: Koehler M. G. , Grigoras Stelian , Dunn W. J. 
Published: October 2006

AbstractThe relationship between chemical structure of a solute and the logarithm of its partition coefficient (log P) between the aqueous and a nonpolar phase is poorly understood. We have recently shown that the variation in log P data for 50 low molecular‐weight organic solutes in 6 aqueous‐non‐polar solvents is a function of two structural features. The main feature accounts for ≈︁60% of the variation in the log P data, and is uniformly weighted in all 6 nonpolar solvent systems. This suggests that it is related to the aqueous solution properties of the solute. The first feature is termed the isotropic surface area, or the surface area associated with the nonpolar portion of the solute when the solute is considered to be a hydrated complex. The hydrated solute complex is termed a supermolecule with waters of hydration occupying hydrogen bonding sites on the functional groups of the solute. Empirical rules for formation of the super molecule are discussed.In this report the analysis is extended to log P data for 72 solutes in the 6 nonpolar solvent systems. The results of the analysis are essentially unchanged for this more extended data set and the second factor is tentatively identified. The second structural feature accounted for ≈︁35% of the variation in the log P data was not equally weighted in all solvents and is difficult to interpret structurally.
Model Solvent Systems for QSAR Part I. Propylene Glycol Dipelargonate (PGDP). A new Standard Solvent for use in Partition Coefficient Determination
Authors: Leahy David E. , Taylor Peter J. , Wait Alan R. 
Published: October 2006

AbstractData for 216 partition coefficients in propylene glycol dipelargonate (PGDP) are given, along with 80 derived fragment values and a scheme for calculating the p.e. 2 correction from which many more log P values can be derived. PGDP log P and f‐values are contrasted with those of octanol and discussed in terms of the differing balance of proton donor/acceptor properties which these solvents show. It is suggested that PGDP, in conjunction with octanol, can be used as a model solvent probe for membrane binding and transport characteristics in ways that may have special relevance to biological selectivity.
A Pharmacophore Hypothesis for Antidepressant Activity: Accomodation of Viloxazine
Authors: Brown George R. 
Published: October 2006

AbstractIn a previous study of the conformation‐activity relationships of antidepressant drugs a pharmacophore hypothesis was developed. This report shows that an incorrect structure of viloxazine was used to validate the hypothesis and comments on the relevance of the fit of the correct structure of viloxazine to the pharmacophore.
Corchop – an Interactive Routine for the Dimension Reduction of Large QSAR Data Sets
Authors: Livingstone David J. , Rahr Elizabeth 
Published: October 2006

AbstractThe combination of the techniques of QSAR and Computer Chemistry (Quantum and Molecular Mechanics) has led to the generation of very large data sets, in terms of the number of parameters used to characterise the molecules of interest. Although there are techniques which may be used to analyse such data sets, it is recognised that there is considerable redundancy within these data. The computer routine CORCHOP was devised to aid the systematic reduction of such data sets to provide a parsimonius description whilst retaining their intrinsic information content. The use of this technique is illustrated by an example data set of antibacterial quinolones.
Drug Lipophilicity in QSAR Practice: I. A Comparison of Experimental with Calculative Approaches
Authors: Mannhold Raimund , Dross Karl P. , Rekker Roelof F. 
Published: October 2006

AbstractExperimental and calculated data of drug lipophilicity, i.e. octanol/water partition coefficients (log Pobs) and hydrophobic fragmental constants (Σf, C log P) have been compared for the following four groups of drugs: antiarrhythmics (AA), β‐blockers (BB), phenothiazines (PT) and benzamides (BA).Measured log P values indicate significantly varying lipophilicity ranges in the case of these four groups (AA>BB>BA>PT).Comparison of the two calculative approaches with observed log P values yields almost identical qualities. Strongest discrepancies between calculative and experimental data are discussed on the basis of putative experimental pitfalls or in relation to structurally derived miscalculations.
The Electrotopological State: An Atom Index for QSAR
Authors: Hall Lowell H. , Mohney Brian , Kier Lemont B. 
Published: October 2006

AbstractA new characterization of atoms in molecules is introduced as the electrotopological state index, which combines both the electronic character and the topological environment of each skeletal atom in a molecule. The electrotopological state (E‐state) of a skeletal atom is formulated as an intrinsic value Ii plus a perturbation term ΔIi, arising from the electronic interaction within the molecular topological environment of each atom in the molecule. The atom intrinsic value, for first row atoms, is expressed as I = (δv + 1)δ, in which δv and δ are the counts of valence and sigma electrons, respectively, for the atom in the molecular skeleton. The E‐state, Si, for atom i is defined as Si = Ij + ΔIj, where the influence of other atoms on atom i, ΔIi, is given as Σ(Ij — Ij)/rij2; rij is the graph separation between atoms i and j, counted as number of atoms, including i and j. Information in the electrotopological state is revealed by examples of various types of organic structures, including skeletal branching and heteroatom variation. The relation of the E‐state value to NMR chemical shift is demonstrated for a series of carbonyl compounds. QSAR examples are given for hydrazide inhibition of MAO and for receptor binding of β‐carbolines. These examples reveal the power of this approach to QSAR using atom level indexes, computed directly from molecule connection tables, in which it is possible to identify atoms and regions in the molecule which are important for activity.
The EDISFAR Programs. Rational Drug Series Design
Authors: Pastor M. , Alvarez‐Buiila J. 
Published: October 2006

AbstractThe computer package EDISFAR is described. The programs can manage physico‐chemical information from a database (MONOBASE) of the fragment parameters classically used in drug design, providing assistance in the use of the techniques related with the Hansch‐Fujita analysis. The user can make design of exploring series of bioactive compounds, using a great variety of techniques, and once a QSAR model has been obtained, can calculate optimum derivatives using the parameters of the MONOBASE. The program has been designed emphasizing its flexibility, accessibility by the practical chemist, and compatibility with other statistics programs or computers.
Structure‐Toxicity Relationships for α, β‐Unsaturated Alcohols in Fish
Authors: Mekenyan Ovanes G. , Veith Gilman D. , Bradbury Steven P. , Russom Christine L. 
Published: October 2006

AbstractPrevious toxicity testing with fathead minnows (Pimephales promelas) indicated that some unsaturated acetylenic and allylic alcohols can be metabolically activated, via alcohol dehydrogenase, to highly toxic α, β‐unsaturated aldehydes and ketones or allene derivatives. Although several in vivo and in vitro toxicological and biochemical endpoints can differentiate these alcohols by toxic mechanism, the use of stereoelectronic molecular descriptors to discriminate these toxicants, and subsequently to predict potency, had not been previously attempted. Exploration of several descriptors indicated that soft electrophilic characteristics of acetylenic or allylic moieties in the suspected metabolites unambiguously discriminated reactive and narcotic toxicants. The acute toxicity of alcohols acting as narcotics was accurately predicted using an existing quantitative structure‐activity relationship for nonpolar narcosis. The toxicity of alcohols mediated by metabolic activation was estimated quantitatively using acceptor superdelocalizability of specific carbon atoms of the acetylenic or allylic moiety in the putative electrophilic intermediates.
A Rigorous Test for SPARC's Chemical Reactivity Models: Estimation of More Than 4300 Ionization pKas
Authors: Hilal S. H. , Karickhoff S. W. , Carreira L. A. 
Published: October 2006

AbstractIonization pKas for a large set of molecules were calculated using reactivity models developed in the computer program SPARC. SPARC uses relatively simple computational algorithms based on fundamental chemical structure theory to estimate ionization pKas of organic molecules strictly from molecular structure. Molecular structures are broken at each essential single bond into functional units with intrinsic properties. Reaction centers (acid or base) are identified and the impact of appended molecular structure on ionization pKa is quantified by perturbation theory. Resonance, electrostatic, solvation and H‐bonding models have been developed and tested on 4338 pKas for 3685 compounds. The RMS deviation for the acids and the amino reaction center was 0.36 pKa units whereas that for the in‐ring N and = N reaction centers was 0.41. Microscopic ionization constants, zwitterionic constants, isoelectric points, and molecular speciation as a function of pH can be calculated using the SPARC models.
QSAR for Allergic Contact Dermatitis
Authors: Graham Cynthia , Gealy Robert , Macina Orest T. , Karol Meryl H. , Rosenkranz Herbert S. 
Published: October 2006

AbstractAllergic contact dermatitis (ACD) is a widespread concern in which sensitization occurs to low molecular weight chemicals. Currently, animal and human assays are used to identify chemicals with potential to cause ACD. MultiCASE, a computer based structure‐activity relational system was employed to evaluate a data base of contact sensitizers and identify structural determinants (biophores) associated with sensitization. The data base was derived from reports of animal and human studies and consisted of 1034 chemicals of which 317 were classified as sensitizers (extreme, strong, moderate, or weak), 22 chemicals had marginal (questionable) activity, and 695 were inactive. MultiCASE identified 49 biophores with related expanded fragments which accounted for the activity of all active chemicals. The major biophores consisted of: 1) a nitrogen double‐bonded to a carbon or a nitrogen; 2) substituted aromatic structures; 3) thiol and disulfide containing fragments; and 4) electrophilic moieties. Modulators of each biophore, which either augmented or decreased potency, included additional structural fragments, two dimensional distance descriptors, as well as physico‐chemical characteristics. Internal evaluation of the data base indicated the sensitivity was 99.6%, and the specificity of the data set was 99.4%. Prediction of the activity of chemicals not in the learning set gave a concordance of 90.2% with experimental results. These findings demonstrate the ability of MultiCASE to identify contact sensitizers and suggest its ability to screen chemicals for their potential to produce ACD.