bluuebunny/crossref_metadata_2025_split huggingface dataset:
QSAR of Some Antifungal Benzoxazoles and Oxazolo(4,5‐b)pyridines against C. albicans
Authors: Şener Esin , Yalçin I̊smail , Sungur Engin 
Published: October 2006

AbstractA congeneric set of 2,5‐disubstituted benzoxazole (III) and 2‐substituted oxazolo(4,5‐b)pyridine (IV) derivatives 1–46, previously tested for their antifungal activity against C. albicans, were analyzed by quantitative structure‐activity relationship (QSAR) techniques. The activity contributions for either ring system or substituent effects were determined from the correlation equations, and the predictions of the potent antifungally active derivatives were described by the results obtained from the computer‐assisted stepwise regression procedure. The resulting QSAR revealed that oxazolo(4,5‐b) pyridine ring system was more preferable than benzoxazole and the benzyl group at position 2 was more significant than the corresponding phenyl substituent. Although the para substitution of benzyl or phenyl moiety with electron donating/withdrawing groups was neglectable, the nature of the substituents at the 5th position (R1) of the fused ring system was important for the potency. Substituting this position with electron withdrawing groups like nitro produces an increase in the antifungal activity.
A Quantitative Structure‐ Activity Relationship (QSAR) for Prediction of α‐2μ‐Globulin Nephropathy
Authors: Barratt Martin D. 
Published: October 2006

AbstractA number of chemicals induce a toxic syndrome in male rats – referred to as α‐2‐μ‐globulin nephropathy – which is characterized by an accumulation of the urinary protein α‐2‐μ‐globulin in renal lysosomes, subsequent cytotoxicity and cell death. Borghoff et al. [1] measured the binding affinities to α‐2μ‐globulin for a number of molecules and metabolites recognised as causing α‐2μ‐nephropathy and suggested that binding is dependent on both hydrophobic interactions and hydrogen bonding. Binding affinity to α‐2μ‐globulin has been identified as one of the determinants for α‐2μ‐globulin nephropathy. A QSAR based on these data has been derived by multiple regression analysis relating the binding to negative charge density of the binding molecule and its molecular volume. Data of Bomhard et al. [2] correlating aliphatic and alicyclic hydrocarbon structures with ability to induce renal lysosome accumulation in male rats, were analysed by the technique of principal components analysis applied to the molecular volumes and principal inertial axes of alcohols predicted to be derived from the hydrocarbons. Mapping of the first and second principal components showed clustering of molecules relative to their biological activity. A combination of the two QSARs is useful in identifying molecules with a potential to cause α‐2μ‐globulin nephropathy.
Variable Selection in QSAR Studies. II. A Highly Efficient Combination of Systematic Search and Evolution
Authors: Kubinyi Hugo 
Published: October 2006

AbstractRecently two evolutionary strategies for the derivation of regression models, a genetic function approximation and the mutation/ selection algorithm MUSEUM have been described. The MUSEUM (Mutation and Selection Uncover Models) algorithm starts from a model containing 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. Only the “fittest” model is stored and used for further mutation and selection, leading to better and better models. However, the fitness of all models with up to three X variables can be determined much faster by calculation of the correlation coefficients ry.ij and ry.ijk from the partial correlation coefficients ryi, rij, ryj.j, rjk.i and ryk.ij. Using the Selwood data set (n = 31 compounds, k = 53 variables), it is demonstrated that systematic search is the best strategy for regression models with two or three X variables. The variables contained in the best three‐variable models can be selected for further investigation, using the evolutionary approach. With the exception of complex models, containing six and more variables, nearly all relevant regression models are found by this combination of systematic search with the mutation/selection algorithm MUSEUM; the results are obtained in considerably shorter time than by including all variables in the calculations. In addition, systematic search is also a valuable tool for variable selection prior to stepwise regression and PLS analyses.
QSAR in Toxicology. 2. Prediction of Acute Mammalian Toxicity and Interspecies Correlations
Authors: Cronin Mark T. D. , Dearden John C. 
Published: October 2006

AbstractA critical review is given of quantitative structure‐activity relationships (QSAR) for the prediction of mammalian toxicological endpoints. QSAR predictions for mammalian toxicity are generally poorly developed although hydrophobicity correlates well with the toxicity of unreactive chemicals. Interspecies correlations of acute toxicity are discussed and when the mode of toxic action is taken into account these may provide a valuable source of information for comparative toxicity and the potential use of surrogate species for testing.
Application of Alternating Conditional Expectations Method to Quantitative Electronic Structure‐Activity Relationships (QESAR)
Authors: Nguyen‐Cong Vu , Rode Bernd M. 
Published: October 2006

AbstractThe Alternating Conditional Expectations (ACE) algorithm for nonlinear dependence of cytotoxicity on atomic net charges evaluated on the basis of semiempirical SCF‐MO calculations has been applied to a series of 28 quassinoids. The best ACE model found from investigating all possible subsets of electronic descriptors has shown that ACE is a useful tool in quantitative structure‐activity relationship studies.
QSAR in Toxicology. 4. Prediction of Non‐lethal Mammalian Toxicological Endpoints, and Expert Systems for Toxicity Prediction
Authors: Cronin Mark T. D. , Dearden John C. 
Published: October 2006

AbstractA critical review is given of quantitative and qualitative structure‐activity relationships (QSAR) for the prediction of some non‐lethal mammalian toxicological endpoints required for regulatory purposes. QSAR in these areas of toxicology, such as irritation and respiratory allergy, is hindered by a lack of quality in vivo toxicity data to model, and by the mechanisms of action not being fully understood. Much progress has been made though into the prediction of skin sensitisation. Commercially available expert systems based on QSAR for toxicity prediction are also described and evaluated critically. Generally it is considered although some systems are well advanced in particular areas, more work is required to make expert systems sufficiently accurate for reliable toxicity prediction.
Conformational Analysis and 3D QSAR Study on Novel Partial Agonists of 5‐HT3 Receptors
Authors: Bureau R. , Lancelot J. C. , Prunier H. , Rault S. 
Published: October 2006

AbstractA conformational analysis which was carried out by molecular dynamics on novel selective and partial agonists of the 5‐HT3 receptor, led to the definition of the partial agonist pharmacophore for 5‐HT3 receptor. Comparative molecular field analysis was carried out on thirty‐nine piperazino pyrrolo thieno pyrazines. The correlation between steric and electrostatic interactions with biological affinities was observed only when electrostatic partial charges were considered. The generated contour maps particulary defined the importance of two groups: a basic nitrogen and a π system.
Molecular Similarity Determination of Heteroaromatic Ring Fragments Using GRID and Multivariate Data Analysis
Authors: Langer Thierry 
Published: October 2006

AbstractThis study reports on molecular similarity determination for heteroaromatic ring fragments permitting to take into account differences in anchoring positions of such substructures in a given molecule. A total of 72 aromatic moieties (five‐ and six‐membered monocyclic and fused benzoannelated heteroaromatics containing one or two heteroatoms) was characterized by interaction energy calculations using a total of 6 multi atom probes within the GRID program and new QSAR descriptors were generated from principal component analysis of the interaction energy matrices thus obtained. A hierarchical clustering procedure of the obtained principal components as well as applying factorial design criteria allowed partitioning of the heteroaromatic substituents into similar families and permitted a classification of structures according to their molecular similarity. The descriptors now obtained were tested for their prediction capacity using different previously reported datasets of biologically active compounds. The results obtained hereby clearly demonstrate the usefulness of 3D derived descriptors.
QSAR and Molecular Modelling of Catamphiphilic Drugs Able to Modulate Multidrug Resistance in Tumors
Authors: Pajeva Ilza K. , Wiese Michael 
Published: October 2006

AbstractThe Free‐Wilson approach was applied to two groups of catamphiphilic multidrug resistance (MDR) modifiers using classical multiple linear regression (MLR) and genetic algorithms (GA) for feature selection. In the first group (17 thioxanthenes) the side chain length between the ring system and tertiary nitrogen, the type of the tertiary nitrogen substituent and the stereoisomery were found to be significant for anti‐MDR activity both by MLR and GA (r2 = 0.803, predictive power Q2 = 0.652). In the second data set (17 phenothiazines and related drugs) the ring system type, the stereoisomery, the side chain type, and the ring substituent kind in position two contributed significantly (r2 = 0.938 and Q2 = 0.908). The QSAR studies showed a thioxanthene ring with a ‐CF3 substituent in position two, a piperazine moiety with a 4‐bond distance from the ring system and trans‐isomery to be optimal for MDR reversal. Based on these results molecular modeling of trans‐(T) and cis‐flupentixol (C) was performed assuming that the 2 to 3‐fold difference in MDR reversing activity of T compared to C might be related to different preferable conformations in the membrane lipid environment. Among all conformations generated by the SYBYL systematic search routine those comprising local energy minima were selected and optimized with semiempirical quantum chemistry methods. The optimized conformations were compared with 1H‐NMR analysis results on drug conformations in lipid environment, some of them corresponded excellently. The electrostatic and lipophilic fields of T and C were compared to identify molecular properties related to the activity difference. The results demonstrated that T and C could have a different (mirror‐like) orientation entering the lipid bilayer by the ring system suggesting much better fitting of T compared to C to the lipid “MDR‐reversal receptor”.
Correspondence Analysis of the Skin Sensitization Potential of Organic Chemicals
Authors: Cronin Mark T. D. , Dearden John C. 
Published: October 2006

AbstractCorrespondence analysis is a variant of principal component analysis for use with categoric data. It has been applied to structural information describing the frequencies of certain molecular features and the skin sensitization potential of a database of organic compounds. Correspondence analysis allows the graphical study of the interrelationship between the relative frequency of structural features of non, weak, moderate and strong sensitizers and the individual class membership. Structural features resulting in protein reactivity are shown to be strongly associated with strong sensitizers; other features, not related to reactivity, are associated with non, or weak, sensitizers. The analysis also indicates structural features whose description is too vague and needs more refinement.
QSARs with Orthogonal Descriptors on Psychotomimetic Phenylalkylamines
Authors: Mracec Maria , Muresan Sorel , Mracec Mircea , Simon Zeno , Náray‐Szabó Gábor 
Published: October 2006

AbstractMultiple linear regressions have been obtained for 49 psychotomimetic phenylalkylamines. The MTD method has been applied and the MTD parameter was used as steric descriptor. The energy of the lowest unoccupied molecular orbital and the net charges on the phenyl ring atoms (from AMI calculations) have been used as electronic descriptors and logPow, or average electrostatic field as lipophilicity descriptor. Hall and Kier electrotopological state indices were also tested. The descriptors have been scaled to unit and orthogonalized by Randic method. The predictability of the regressions obtained from MTD method have been checked by a method similar to cross‐validation from CoMFA method. MTD has been identified as the dominant descriptor by Randic orthogonalization. The best model has been obtained with MTD and electrotopological state indices, showing the importance of the steric and electronic properties for the interaction at the receptor site level.
Structure‐Activity Relationships of a Steroid Family using Quantum Similarity Measures and Topological Quantum Similarity Indices
Authors: Lobato Miquel , Amat Lluís , Besalú Emili , Carbó‐Dorca Ramon 
Published: October 2006

AbstractThis work will try to study an application example of quantum similarity measures, in order to determine quantitative relationships between the structure and biological activity for a family of steroids. The studied family is composed of 31 molecules, and the property analyzed is the affinity to the corticosteroid binding globulin receptor. Two methodologies have been chosen to perform QSAR on the mentioned steroid set. Both methodological frameworks are based on quantum similarity measures, the first one is based on the use of similarity indices as molecular descriptors and the second methodology uses quantum similarity topological indices for the same purpose. The use of molecular descriptors, obtained from quantum similarity topological indices constructs, constitutes a new technique developed recently in our laboratory to be used in QSAR in close relationship with the already explored field of quantum similarity measures. Results become comparable to other 3D‐QSAR techniques.
On Flexible Fitting Using The Molecular Similarity Index. A neural network analysis for antileishmaniasis compounds
Authors: Montanari Carlos A. , Tute Michael S. 
Published: October 2006

AbstractPentamidine analogues bind to the minor groove by using the pharmacophoric conformation as being isohelical do DNA. A QSAR model has disclosed three physiochemical descriptors as being important for such compounds against Leishmania mexicana amazonensis: Clog P, electrotopological index and Carbo similarity index. A comparison of the QSAR equation derived from multiple regression analysis, MRA, and the one from neural network analysis, NN, shows the latter to be of higher significance.
ToF‐SIMS imaging of lipids in cell membranes
Authors: Johansson Björn 
Published: October 2006

AbstractSecondary ion mass spectrometry (SIMS) has been in use in biomedical imaging for more than three decades and has resulted in some important biomedical discoveries. However, SIMS has not become a part of most biologists' instrumentarium, even though this method enables chemical analysis in the context of anatomical regions and even subcellular structures. Secondary ions characteristic of a range of important lipids can now be efficiently produced from cell membranes and imaged by SIMS. Recently developed ion sources producing cluster primary ions, in combination with modern, sensitive time‐of‐flight (ToF) mass analyzers, have enabled this new bioimaging method. This article briefly describes cell membranes and their lipids as well as the new primary ion sources, and moves on to review recent biomembrane studies by time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) and related methods. Further refinements in equipment and other methodology that will facilitate the use of SIMS in biomembrane studies are suggested. It is concluded that ToF‐SIMS mass spectrometry for membrane and other biology applications is definitely on the rise. Copyright © 2006 John Wiley & Sons, Ltd.
Rapid radiation degradation in the XPS analysis of antibacterial coatings of brominated furanones
Authors: Al‐Bataineh Sameer A. , Britcher Leanne G. , Griesser Hans J. 
Published: October 2006

AbstractBrominated furanones are promising antibacterial compounds, both in solution and immobilized on solid surfaces, and there is interest in their utilization as protective coatings on biomedical devices to combat device‐centered infections. The rational design and optimization of antibacterial furanone coatings requires detailed spectroscopic surface characterization of the coatings produced and correlation of surface analysis data with antibacterial performance. However, as reported in this study, the extreme sensitivity of brominated furanones to radiation damage in the course of XPS analysis greatly complicates characterization. Our data show that rapid degradation occurs, as shown by the emergence of a signal assignable to Br− ion in the Br 3d spectrum. This Br− is water soluble as shown by washing experiments, whereas the CBr signal does not become reduced during washing, consistent with covalent interfacial immobilization of the furanone molecules. Furanone molecules were immobilized onto two different hydrogel interlayers (polyacrylic acid and polyethylene oxide (PEO)), and XPS analyses show that the interlayers did not suffer significant radiation degradation; the damage is limited to the furanone molecules. The results of this study may assist in XPS analyses of other brominated compounds on surfaces; the possibility of Br− ions deriving from XPS analysis–damage must be investigated before assigning their generation to side reactions in the coating or surface‐modification procedure. Copyright © 2006 John Wiley & Sons, Ltd.
The application of atomic force microscopy force measurements to the characterisation of microbial surfaces
Authors: Wright Chris J. , Armstrong Ian 
Published: October 2006

AbstractThe interaction of microbes and subsequent development of biofilms at surfaces has far‐reaching consequences in bioprocess engineering, agriculture, medicine and dentistry. Thus, the microbial surface has been the focus of wide scientific investigation. However, only recently has technology permitted quantitative study of the molecular interactions that govern the interactions of microbes. One such technology is atomic force microscopy (AFM) that not only permits the high resolution imaging of microbial surfaces but also the direct measurement of molecular forces and physical properties found at the microbial surface. This review highlights the current development of AFM force measurements and how these may be applied to microbial cell surfaces. The refinement of the AFM force measurement technique for characterising microbial surfaces will be discussed with reference to selected studies from the author's laboratory and key results from other research teams. The review will demonstrate how the application of the AFM techniques of single‐molecule force spectroscopy, functionalised tips, cell probes and lateral force measurement to microbial surfaces has provided exciting and unique insights into the microbial surface and its interactions. Copyright © 2006 John Wiley & Sons, Ltd.
Acute toxicity tests using rotifers. III. Effects of temperature, strain, and exposure time on the sensitivity of Brachionus plicatilis
Authors: Snell Terry W. , Moffat Brian D. , Janssen Colin , Persoone Guido 
Published: October 2006

AbstractAs part of the development of a standardized acute toxicity test, the effect of cyst age, strain, temperature, and exposure time on the toxicity of 21 chemicals to the estuarine rotifer Brachionus plicatilis was investigated. Toxicity was chemical specific, with LC50s ranging from 0.061 mg · L−1 for mecury to 598 mg · L−1 for 2,4‐dichlorophenoxyacetic acid. Intralaboratory coefficients of variation averaged 11%, at least three times lower than for other aquatic invertebrate acute tests. The age of rotifer cysts stored up to 27 months had no effect on the sensitivity of test animals, but significant differences in sensitivity were detected among rotifer strains. Test temperatures of 25, 30, and 35°C generally yielded lower LC50s than at 20°C. LC50s decreased by 80–90% for cadmium and pentachlorophenol when toxicant exposure time was increased from 24 to 72 h. Life table analysis of rotifer survival in the controls revealed that 72 h is the longest acute test possible without feeding. A comparison of the sensitivity of the rotifer test to that of sea urchin (Arabacia punctulata) early embryo, sea urchin sperm cell, Microtox®, and Mysidopsis bahia tests revealed comparability for several compounds. However, no species is consistently the most sensitive to all compounds.
Implications of botulism outbreaks in gulls (Larus ridibundus) on the Watershed Management of Lake Kinneret (Israel)
Authors: Gophen M. , Cohen A. , Grinberg K. , Pokamunski S. , Nili E. , Wynne D. , Yawetz A. , Dotan A. , Zook‐Rimon Z. , Ben‐Shlomo M. , Ortenberg Z. 
Published: October 2006

AbstractLake Kinneret (Israel), which currently supplies 30% of the national water demands (of which 50% is for domestic purposes), is also utilized for commercial fishery, recreation, and tourism. The measures taken to prevent pollution include, among others, sewage and fish pond waste removal, and burial of industrial and household solid wastes at established garbage dumps. On January 13, 1985, hundreds of dead and moribund gulls (Larus ridibundus) were observed on the shoreline and water surface at the northwest part of the lake, and around the northern garbage dump site. Sick birds exhibited signs that the nervous system was involved, i.e., paralysis of the wings and of the feet, and limberneck. Routine analyses ruled out the possibility that the poisoning was due to pesticides or an infective agent. Botulism intoxication was suspected and type C‐botulism toxin was identified in the serum of moribund birds. This is the first record of a botulism outbreak in waterfowl in Israel. The total mortality was approximately 3000–4000 gulls, of which 1200 dead birds were collected and burnt. Investigations revealed that at a garbage dump situated in the vicinity of the lake, waste products of a chicken slaughter house were not buried as required by formal regulations. Examination of lake water, sediments, and vegetations for possible contamination by botulism toxin were negative. The implications of the outbreak on the environment are discussed.