bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aqueous degradation of isoflavonoids in an extract of Millettia thonningii (Leguminosae) which is larvicidal towards schistosomes
Authors: Perrett Sheena , Whitfield Philip J. 
Published: October 2006

AbstractA chloroform extract of the seeds of the West African legume Millettia thonningii has been shown to kill the snails which transmit the schistosomiasis and also the larvae of the parasite itself. This study examines the bioactivity of the chloroform extract of M. thonningii in aqueous non‐sterile conditions. Suspensions of the extract in water maintained larvicidal activity for long periods. HPLC analysis showed that over a period of 4 weeks in aqueous suspension, degradation of two of the compounds present, the isoflavonoids alpinumisoflavone and 4′‐methylalpinumisoflavone, occurred and bioactivity was eventually lost, indicating that these compounds are probably responsible for the bioactivity. These isoflavonoids are thought to act via inhibition of electron transport.
Moderate cytotoxicity of proanthocyanidins to human tumour cell lines
Authors: Kolodziej H. , Haberland C. , Woerdenbag H. J. , Konings A. W. T. 
Published: October 2006

AbstractIn the present study the cytotoxicity of 16 proanthocyanidins was evaluated in GLC4, a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. With IC50 values ranging from 18 to >200 μM following continuous incubation, the proanthocyanidins examined possess only moderate to low cytotoxicity. The highest cytotoxicity was found in a series of galloylated proanthocyanidins. An increase in the number of galloyl substituents increased cytotoxicity. Simple proanthocyanidins possess low cytotoxicity, that was independent of the stereochemistry. Compounds with doubly linked units had negligible cytotoxic effects, even at 200 μM, the highest concentration tested.
In vivo inhibitory effects of arjunolic acid derivatives on two‐stage carcinogenesis in mouse skin
Authors: Diallo B. , Vanhaelen‐Fastré R. , Vanhaelen M. , Konoshima T. , Takasaki M. , Tokuda H. 
Published: October 2006

AbstractIn a previous study, arjunolic acid (1) isolated from Cochlospermum tinctorium and its hemisynthetic derivatives 2, 3 and 4 were shown to exhibit in vitro inhibitory effects on Epstein—Barr virus (EBV) activation. Compounds 3 and 4, which showed the strongest inhibitory activities, were further prepared from arjunolic acid isolated from Mitragyna ciliata; they were tested in vivo on a two‐stage carcinogenesis assay in mouse skin, using dimethyl‐benz[a]anthracene (DMBA) as initiator and 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) as promoter. The activities were evaluated by both rate (%) of papilloma‐bearing mice and average number of papillomas per mouse and compared with the control. In the group of mice treated with 3 and 4, the occurrence of papillomas was delayed, compared with the results of the control; with derivative 4, papillomas occurred in 100% animals only at week 15. These results suggest that arjunolic acid derivatives could be valuable compounds as antitumour‐promoters.
Preliminary studies on the hydroalcoholic extract of the root of Cissampelos sympodialis Eichl in guinea‐pig tracheal strips and bronchoalveolar leucocytes
Authors: Thomas G. , Araújo C. C. , Agra M. De F. , Diniz M. De F. F. , Bachelet M. , Vargaftig B. B. 
Published: October 2006

AbstractThe aqueous fraction of the ethanol extract of the root of Cissampelos sympodialis, reduced the spontaneous tone, and inhibited the contractions induced by submaximal concentrations of carbachol, histamine, prostaglandin F2α and substance P, in guinea‐pig tracheal preparations. The fraction was approximately equipotent to aminophyl‐line and the IC50 values of the above agents varied from 13.9 to 95.5 μg/mL, depending on the agonist used. In concentrations ranging from 1–100 μg/mL, the fraction also increased the intracellular levels of cyclic adenosine monophosphate in guinea‐pig bronchoalveolar leucocytes. It is proposed that the combined effects on smooth muscles and on leucocytes indicate a pharmacological basis for the use of the plant in asthma.
Effect of picroliv on regeneration of liver after partial hepatectomy in rats
Authors: Saksena Seema , Rastogi Ravi , Garg N. K. , Dhawan B. N. 
Published: October 2006

AbstractAfter partial hepatectomy in rats certain biochemical parameters in liver registered a maximal increase at varying periods of time, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) (6 h), lipid peroxides (12 h); DNA, RNA (24 h) and acid ribonuclease, acid phosphatase (48 h). In contrast, other parameters registered a maximal decrease after 6 h (glycogen) or 24 h (total proteins, cytochrome P450 and cytochrome b5). Subsequently, all these parameters started recovering towards their normal values which were attained in all parameters measured except RNA, glycogen, cytochrome h5 and acid ribonuclease. When partial hepatectomy was performed in rats fed 12 mg/kg body wt picroliv (an iridoid glycoside fraction of Picrorhiza kurroa) once daily for 7 days before killing, there was no significant difference in the time or degree of maximal changes but the rate of recovery in most of the biochemical parameters was faster. These results indicate that picroliv stimulated regeneration of liver.
Synthesis of [4,5‐3H]‐Exo‐3,6‐epoxyhexahydrophthatic anhydride
Authors: Wu Dezhu , Zheng Zongqi , Wang Guangsheng 
Published: October 2006

AbstractA convenient two‐step synthesis of [4,5‐3H]‐Exo‐3,6‐epoxyhexahydrophthatic anhydride ((4,5‐3H)‐norcantharidin) consists of furan reacting with maleic anhydride to form dehydronorcantharidin. Then addition of tritium to dehydronorcantharidin with catalyst to form [4,5‐3H]‐norcantharidin. The specific activity and radiochemical purity were 56 Ci/mmol and 98%, respectively.
Antihistamine effects of an ethanol extract from the white petals of Impatiens balsamina L
Authors: Fukumoto Hisae , Isoi Koichiro , Semma Masanori , Ishiguro Kyoko 
Published: October 2006

AbstractUsing blood pressure (BP) monitoring in ddY Mice administered exogenous histamine, we tried to characterize the antianaphylactic mechanisms of a 35% ethanol extract (IB) from the petals of Impatiens balsamina L. Histamine was suggested to act as an initiator of anaphylactic hypotension in mice. IB could incompletely inhibit the first stage of hypotension caused by histamine. The antianaphylactic effect of IB was demonstrated to be different from that of diphenhydramine (DPH) a typical H1 blocker.
Spasmolytic actions of warifteine, a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl. (menispermaceae)
Authors: de F. Cǒrtes S. , de Alencar J. L. , Thomas G. , Filho J. M. Barbosa 
Published: October 2006

AbstractWarifteine, a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl., produced a reversible, nonspecific and noncompetitive antagonism of histamine, carbachol and bradykinin induced contractions of the guinea‐pig ileum. The corresponding pD'2 values (mean±SE) were 4.90±0.15, 4.95±0.20 and 5.03±0.11. Warifteine also antagonized oxytocin and bradykinin induced contractions of the rat uterus in a similar manner with pD'2 values of 4.30±0.26 and 3.76±0.06 respectively. In the guinea‐pig trachea, the alkaloid inhibited spontaneous tone (IC50, 1.1 × 10−5M) as well as carbachol induced sustained contractions (IC50, 2.9 × 10−5M). As warifteine antagonized KCI induced contractions of the guinea‐pig ileum (pD'2 value 4.57±0.10), inhibition of Ca++ influx through voltage operated Ca++ channels may be partially responsible for its antispasmodic activity. However, the reported local anaesthetic property of warifteine may not contribute to the observed muscle relaxation as procaine failed to reduce the spontaneous tone or consistently antagonize carbachol induced contractions of the trachea and was inactive in inhibiting voltage operated Ca++ channels in the ileum.
A Free‐Wilson Analysis of 5β,14β‐Androstane Derivatives Inhibiting the Na/K‐ATPase from Human Heart
Authors: Schönfeld Werner , Repke Kurt R. H. 
Published: October 2006

AbstractA Free‐Wilson analysis of 95 digitalis‐like steroids inhibiting the Na/K‐ATPase is presented. The chosen parent structure – 5β,14β‐androstane‐3β,14‐diol – was varied at 12 individual substitution sites. The high significance of the multiple regression of the data obtained with the great majority of the derivatives tested revealed the general applicability of the additivity model, allowing the prediction of the potency of hypothetical compounds from the derived 57de novosubstituent constants. Derivatives carrying voluminous substituents at C3 or C17, in which the cis/trans/cis‐junction of the steroid rings were altered, disclosed incompatibilities with the model.
Model‐Based Relation between Physicochemical Properties, Uptake and Uncoupling Effect of Carbonylcyanide Phenylhydrazones on Oxidative Phosphorylation at Cellular Level
Authors: Šturdik Ernest , Baláz Štefan , Ďurčová Edita , Šturdiková Mária , Sulo Pavol , Antalik Marián , Mikeš Vladimír , Dadák Vladimír 
Published: October 2006

AbstractAnalysis of uptake‐lipophilicity profiles of carbonylcyanide R‐phenylhydrazones (RC6H4NHNC(CN)2) in Paracoccus denitrificans and leukemic P‐388 cells showed that in early stages the drug distribution proceeds as simple diffusion in a multi‐phase system. After 10 min of partitioning only attainment of a lipophilic‐hydrophilic equilibrium was detected without observable chemical modification of the compounds. This fact allowed for straightforward formulation of two models for uncoupling of cellular oxidative phosphorylation, one based on protonophoric mechanism and the other involving covalent modification of energy transforming membrane proteins as the key step. Moreover, it enabled us to describe the dependence of uncoupling activity on lipophilicity using the uptake data and, thus, to reduce the number of adjustable parameters. The former (protonophoric) model exhibited a significantly better agreement with the experimental data in both biological systems.
QSAR and Multivariate Data Analysis of Amphiphilic Benzylamines and their Interaction with Various Phospholipids Determined by Different Methods
Authors: Seydel J. K. , Cordes H.‐P. , Wiese M. , Chi H. , Croes N. , Hanpft R. , Lüllmann H. , Mohr K. , Patten M. , Padberg Y. , Lüllmann‐Rauch R. , Vellguth S. , Meindl W. R. , Schönenberger H. 
Published: October 2006

AbstractAmphiphilic drugs of various structures are known to interact with phospholipids. Simple benzylamines have been used as probes to test the structural influence on the degree of interaction. This interaction has been quantified with various methods as for example NMR‐binding measurements, scanning calorimetry, inhibition of Ca++‐incorporation, negative inotropic effect and antimycobacterial activity.Multiregression and multivariate data analysis have been performed and the results are discussed.
Hydrophobicity and Tumor Promoting Activity of Phorbol Esters
Authors: Rippmann Friedrich 
Published: October 2006

AbstractPhorbol esters are polyfunctional agents which influence the carcinogenic process via a receptor mechanism. Two structural elements of phorbol esters seem to be responsible for tumor promoting activity. One element is formed of certain hydrophilic groups which are supposed to be responsible for the specific receptor binding. The other element consists of hydrophobic groups which should rather unspecifically be responsible for partition and transport between biological phases. In order to differentiate between these two structural elements, the numerical relativ tumor promoting activity of phorbol diesters (a new activity in QSAR) was calculated from rodent skin painting experiments and its dependence from hydrophobicity was modeled using the parabolic and the bilinear model. The results show that the tumor promoting activity of aliphatic phorbol 12,13‐diesters can adequately be described by hydrophobicity only. This indicates that the structural element aliphatic‐12,13‐diesters is rather unspecifically responsible for partition and transport between biological phases. A medium hydrophobicity caused by aliphatic ester chains in position 12 and 13 of phorbol is a sufficient condition for high promoting activity as long as the other hydrophilic groups are not removed, acylated or otherwise changed.
Pharmacophore Identification in Amnesia‐Reversal Compounds Using Conformational Analysis and Chemometric Methods
Authors: Cosentino Ugo , Moro Giorgio , Pitea Demetrio , Todeschini Roberto , Brossa Simonetta , Gualandi Federico , Scolastico Carlo , Giannessi Fabio 
Published: October 2006

AbstractThe conformational features of ten known amnesia reversal compounds were analyzed by the molecular mechanics calculations with the aim of identifying a common spatial disposition of the polar functional groups present in all the molecules (a N‐C=O amidic group and a X‐C=O group, with X = O, N). Principal component analysis (PCA) led to the identification of three interatomic distances able to provide all the information necessary to describe the relative spatial disposition of the two functional groups. Cluster analysis was then performed to group the minimum energy conformations according to the values of those distances. Clusters were analyzed to single out those containing conformations of the maximum number of active compounds. This procedure permitted the finding of several acceptable pharmacophore models. The influence on results by the dissociated/undissociated forms of carboxylic compounds presented in the data set is also discussed. Two potent prolyl endopeptidase (PEP) inhibitors showing strong anti‐amnesic effect were also included in the study. The results suggest that the common biological activity between these classes of compounds could be interpreted on the basis of the common spatial disposition of the investigated functional groups.
Induction of Cytochrome P450 by Barbiturates in Chick Embryo Hepatocytes: A Quantitative Structure‐Activity Analysis
Authors: Hansch Corwin , Sinclair Jacqueline F. , Sinclair Peter R. 
Published: October 2006

AbstractIn cultured chick embryo hepatocytes, induction of cytochrome P450 by nine 5,5‐substituted barbiturates was analyzed for a quantitative structure‐activity relationship. The data led to the following equation:
Log 1/C = 1.02 (±0.16) log P + 2.75 (±0.28), r = 0.984
where C is the concentration that caused a 50% increase in cytochrome P450, P is the partition coefficient between octanol and water, and r is the correlation coefficient. The results suggest that the potency of the barbiturates was directly related to their hydrophobicity.
Quantitative Structure‐Activity Relationship (QSAR) Studies Using Electronic Descriptors Calculated from Topological and Molecular Orbital (MO) Methods
Authors: Gombar Vijay K. , Enslein Kurt 
Published: October 2006

AbstractThe performance of certain electronic descriptors rapidly calculated by a topology‐based method has been compared with those computed by time‐consuming MO methods for QSAR studies on mutagenicity of a set of triazenes. The highly significant correlations obtained in the two cases not only are of excellently comparable statistical quality but also support the same mechanism of mutagenicity.
A Structure‐Activity Relationship for the Binding of Acridine‐4‐Carboxamides to DNA
Authors: Moyer Susan R. , Jurs Peter C. 
Published: October 2006

AbstractThe DNA binding constants for a series of acridine‐4‐carboxamides were modeled using quantitative structure‐activity relationship methodology. In particular, a data set containing 52 acridine derivatives along with their DNA binding constants for the poly(dA‐dT) and poly(dG‐dC) sites of DNA was obtained from the literature. The descriptors which were calculated and ultimately used in the regression models were designed to encode a specific binding site model which had previously been proposed in the literature. Since it is believed that the acridines interact with the DNA by intercalation, surface area and charge descriptors were calculated for regions of the acridine backbone which are theorized to be in close proximity to the DNA chain. The ability of these descriptors to successfully model the DNA binding constants for the data set supports the binding model which was previously proposed.
3‐Hydroxy‐3‐Methylglutaryl‐Coenzyme A Reductase: Molecular Modeling, Three‐Dimensional Structure‐Activity Relationships, Inhibitor Design
Authors: Motoc I. , Sit S. Y. , Harte W. E. , Balasubramanian N. , Wright J. J. 
Published: October 2006

AbstractThe 9,9‐bis(4‐fluorophenyl)‐3,5‐dihydroxy‐8‐(substituted)‐6, 8‐nonadienoic acid analogues represent a novel class of HMG‐CoA reductase inhibitors developed in our laboratories. We delineate from inhibitory potency values the main topographical and physicochemical features of the binding site probed by substituents attached to the C8 position of the analogues. Using a combination of receptor mapping and 3D‐QSAR techniques, it was possible to determine a logical candidate for the conformation of the inhibitor bound to the receptor and to derive a reliable 3D‐QSAR which relates the HMG‐CoA reductase inhibitory potency to the shape and size of both the binding site and C8‐substituent of the inhibitor. We show that the 3D‐QSAR derived here affords predictive utility.
Using Theoretical Descriptors in Quantitative Structure‐Activity Relationships: Comparison with the Molecular Transform
Authors: Famini George R. , Kassel Ronald J. , King James W. , Wilson Leland Y. 
Published: October 2006

AbstractA variety of techniques and methodologies are currently being used in quantitative structure‐activity relationships (QSAR). A major difficulty with past relationships has been the use of a parameter sets which cannot be applied uniformly to a wide range of properties and data sets. The development of the Linear Solvation Energy Relationship by Kamlet and Taft, and our development of the Theoretical Linear Solvation Energy Relationship (TLSER) have attempted to overcome this principal difficulty by employing a standard parameter set for every correlation. Another methodology that has also proven successful in this regard is the use of topological indices to correlate a variety of properties. This paper compares the TLSER with one such index, the molecular transform. In addition, we show the high correlative capability of the TLSER methodology with the minimum blocking concentration for a set of 36 local anesthetics.
A QSAR Approach to the Study of Structural Requirements of Muscarinic Receptor Ligands Part I: Agonists
Authors: Pratesi P. , Caliendo G. , Silipo C. , Vittoria A. 
Published: October 2006

AbstractThis report examines the development of quantitative structure‐activity relationships (QSAR) in the analysis of ligand muscarinic receptor interactions. Several sets of agonists acting on different tissues (distinct receptor subtypes) are considered. It is shown that QSAR may represent a suitable tool to increase the general understanding of the nature of ligand interactions at receptor sites. The points discussed in the paper are to draw attention to the development of correlations between biological affinity constants and molecular architecture of the ligands which are essential for deriving refined concepts on the topology of muscarinic receptor sites.
A QSAR Approach to the Study of Structural Requirements of Muscarinic Receptor Ligands Part II: Antagonists
Authors: Pratesi P. , Caliendo G. , Silipo C. , Vittoria A. 
Published: October 2006

AbstractSeveral sets of ligands acting as antagonists at muscarinic receptor sites are considered by means of QSAR approach. Although the confusing role of the collinearity among vectors associated with physicochemical parameters makes it sometimes difficult to evaluate the quality of structure‐activity correlations, the points discussed in the paper are to draw attention to the development of correlations between biological affinity constants and structural features of antagonists. The results obtained are compared to those relative to an analogous study on the agonists. It is shown that correlation equations are essential for deriving refined concepts on the topology of muscarinic receptor sites.
QSAR: Conceptions and Misconceptions
Authors: Ariëns Everd J. 
Published: October 2006

AbstractThe basis for QSAR‐studies on drugs, pesticides and other xenobiotics is the maxim: “Exposure of nature (including man) and its environment to xenobiotics (including drugs) is only justified if the desirable actions adequately compensate for the undesirable actions and the never fully excluded risks”.QSAR requires a clearcut congenerity which implies: a 3‐dimensional homology of the various molecular fragments in the chemical framework in the series of compounds “compared”. QSAR in drug etc. development has to comprise activity as well as selectivity. QSAR in relation to drug‐receptor interaction requires restriction to isoregional and isochiral structural variation in the group of congeneric agents compared. In QSAR based on the integral approach, e.g. fractional constants related to lipophilicity or molecular connectivity, overall qualities such as passive membrane penetration and tissue accumulation play a predominant role.QSMR – Quantitative Structure‐Metabolism Relationship – is an essential factor in in vivo QSAR.Eudismic analysis is a prerequisite for QSAR dealing with CCD's, CCP's – Composite Chiral Drugs or Pesticides.Disregard of isomeric ballast invalidates QSAR on chiral agents.
Molecular Modelling Studies on 1,4‐Dihydropyridines Acting at the Ca‐Channel
Authors: Höltje H.‐D. 
Published: October 2006

AbstractUsing molecular modelling techniques, we have compared structural features of a series of 1,4‐dihydropyridine calcium‐channel blockers. Computer graphics modelling suggests that the agonistic as well as the antagonistic behaviour is controlled by substituents at the C‐5 of the DHP‐system, whereas differences in phenyl ring substitution may influence tissue selectivity and negative inotropic activity of the compounds.
Generating Optimal Linear PLS Estimations (GOLPE): An Advanced Chemometric Tool for Handling 3D‐QSAR Problems
Authors: Baroni Massimo , Costantino Gabriele , Cruciani Gabriele , Riganelli Daniela , Valigi Roberta , Clementi Sergio 
Published: October 2006

AbstractAn advanced variable selection procedure, called GOLPE, aimed at obtaining PLS regression models with the highest prediction ability is presented and illustrated with an application in 3D‐QSAR. Key steps in the procedure are a preliminary variable selection by means of a D‐optimal design in the loading space, and an iterative evaluation of the effects of individual variables on the model predictivity based on the validation of a number of reduced models, on variables combinations selected according to a FFD strategy.The procedure is successfully applied to a real 3D‐QSAR case study: the results obtained by GOLPE are compared with those obtained by CoMFA and found to be in good agreement in terms of variable importance, but with a much higher prediction ability. Accordingly, the results encourage to think that it might be used within the CoMFA framework in the place of the present PLS version there, or in CoMFA‐like studies on the structures generated by GRID probes.