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Relationship Study (relationship + study)
Kinds of Relationship Study Selected AbstractsQuantitative Structure,Activity Relationship Study on Fish Toxicity of Substituted BenzenesMOLECULAR INFORMATICS, Issue 8 2008Zhiguo Gong Abstract Many chemicals cause latent harm, such as erratic diseases and change of climate, and therefore it is necessary to evaluate environmentally safe levels of dangerous chemicals. Quantitative Structure,Toxicity Relationship (QSTR) analysis has become an indispensable tool in ecotoxicological risk assessments. Our paper used QSTR to deal with the modeling of the acute toxicity of 92 substituted benzenes. The molecular descriptors representing the structural features of the compounds were calculated by CODESSA program. Heuristic Method (HM) and Radial Basis Function Neural Networks (RBFNNs) were utilized to construct the linear and the nonlinear QSTR models, respectively. The predictive results were in agreement with the experimental values. The optimal QSTR model which was established based on RBFNNs gave a correlation coefficient (R2) of 0.893, 0.876, 0.889 and Root-Mean-Square Error (RMSE) of 0.220, 0.205, 0.218 for the training set, the test set, and the whole set, respectively. RBFNNs proved to be a very good method to assess acute aquatic toxicity of these compounds, and more importantly, the RBFNNs model established in this paper has fewer descriptors and better results than other models reported in previous literatures. The current model allows a more transparent chemical interpretation of the acute toxicity in terms of intermolecular interactions. [source] Use of Topological Indices of Organic Sulfur Compounds in Quantitative Structure-Retention Relationship StudyMOLECULAR INFORMATICS, Issue 9 2005F. Safa Abstract Structure-gas chromatographic retention index models were developed for some organic sulfur compounds at four different temperatures (60, 80, 100 and 120,°C) using only topological descriptors. At first, regression models were generated for each temperature separately with high values of multiple correlation coefficient and Fisher-ratio statistics. The results of cross validation test using leave-one-out (Q2,0.956) and leave-two-out (Q2,0.953) methods showed good predictive ability of the models developed. Then, a single combined quantitative structure-retention relationship model, added temperature as a parameter, was also developed for all the temperatures, showing good statistical parameters (R=0.991 and F=728.474). The stability and validity of the combined model were verified by both internal (Q2>0.970) and external validation (Q=0.993) techniques. The results of the study indicated the efficiency of the classical topological descriptors in simultaneous prediction of retention index values of sulfur compounds at different temperatures. The topological descriptors well covered the molecular properties known to be relevant for gas chromatographic retention data, such as molecular size and degree of branching. [source] Structure-hepatoprotective activity relationship study of sesquiterpene lactones: A QSAR analysisINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 1 2009Yuliya Paukku Abstract This study has been carried out using quantitative structure-activity relationship analysis (QSAR) for 22 sesquiterpene lactones to correlate and predict their hepatoprotective activity. Sesquiterpenoids, the largest class of terpenoids, are a widespread group of substances occurring in various plant organisms. QSAR analysis was carried out using methods such as genetic algorithm for variables selection among generated and calculated descriptors and multiple linear regression analysis. Quantum-chemical calculations have been performed by density functional theory at B3LYP/6-311G(d, p) level for evaluation of electronic properties using reference geometries optimized by semi-empirical AM1 approach. Three models describing hepatoprotective activity values for series of sesquiterpene lactones are proposed. The obtained models are useful for description of sesquiterpene lactones hepatoprotective activity and can be used to estimate the hepatoprotective activity of new substituted sesquiterpene lactones. The models obtained in our study show not only statistical significance, but also good predictive ability. The estimated predictive ability (r) of these models lies within 0.942,0.969. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source] Quantitative structure,activity relationship study on the inhibitors of fatty acid amide hydrolaseJOURNAL OF CHEMOMETRICS, Issue 9 2010Peng Lu Abstract A quantitative structure activity relationship (QSAR) analysis was performed on the values of a series of fatty acid amide hydrolase (FAAH) inhibitors. Six molecular descriptors selected by CODESSA software were used as inputs to perform heuristic method (HM) and support vector machine (SVM). The results obtained by SVM were compared with those obtained by the HM. The root mean square errors (RMSEs) for the training set given by HM and SVM were 0.555 and 0.404, respectively, which shows that the performance of the SVM model is better than that of the HM model. This paper provides a new and effective method for predicting the activity of FAAH inhibitors. Copyright © 2010 John Wiley & Sons, Ltd. [source] Synthesis and biological evaluation of carbon-11-labeled acyclic and furo[2,3-d]pyrimidine derivatives of bicyclic nucleoside analogues (BCNAs) for structure,brain uptake relationship study of BCNA tracersJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2008Satish K. Chitneni Abstract We reported earlier on radiolabeled alkoxyphenyl bicyclic nucleoside analogues (BCNAs) as potential positron emission tomography (PET) reporter probes for imaging of varicella zoster virus thymidine kinase (VZV-tk) gene in vivo. Despite their favorable physicochemical properties, these tracers are not taken up in the brain in mice. In order to probe the role of the deoxyribose sugar moiety in blood-brain barrier (BBB) penetration of these molecules, we have synthesized and evaluated a carbon-11-labeled acyclic bicyclic nucleoside derivative ([11C]-10) where the 2,-deoxyribose sugar is replaced with a (2-hydroxyethoxy)methyl group and [11C]-12, which has no sugar moiety but a [11C]methyl group on the N-3 position of the pyrimidine ring. Methylation was achieved on the phenol ([11C]-10) or the N-3 position ([11C]-12) using [11C]methyl triflate (radiosynthesis). The (non-radioactive) acyclic O -methyl derivative 10 has rather poor affinity for the enzyme VZV-TK in vitro (IC50: 430,µM), compared with the moderate affinity of the BCNA-base N -methyl derivative 12 (IC50: 79,µM). In normal mice, none of the two tracers ([11C]-10 or [11C]-12) showed significant uptake in the brain, suggesting that compounds containing a furo[2,3- d]pyrimidine system do not cross the BBB. Copyright © 2008 John Wiley & Sons, Ltd. [source] Prediction of flammability characteristics of pure hydrocarbons from molecular structuresAICHE JOURNAL, Issue 3 2010Yong Pan Abstract A quantitative structure-property relationship study is performed to develop mathematical models for predicting the flammability characteristics of pure hydrocarbons. The molecular structures of the compounds are numerically represented by various kinds of molecular descriptors. Genetic algorithm based multiple linear regression is used to select most statistically effective descriptors on the flash point, the autoignition temperature, and the lower and upper flammability limits of hydrocarbons, respectively. The resulted models are four multilinear equations. These models are very simple and can predict the flash point, the autoignition temperature, and the lower and upper flammability limits for the test set with average absolute errors of 5.41 K, 28.00 K, 0.044 vol %, and 0.503 vol %, respectively. The models are further compared with other published method and are shown to be more superior. The proposed method can be used to predict the flammability characteristics of hydrocarbons from the knowledge of only the molecular structures. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Synthesis and biological properties of the seven alanine-modified analogues of the marine cyclopeptide hymenamide CJOURNAL OF PEPTIDE SCIENCE, Issue 8 2002Assunta Napolitano Abstract The synthesis and biological activity of the marine cyclopeptide hymenamide C(1), showing an inhibitory effect on human neutrophil elastase degranulation release, were recently described. Based on this result, it was decided to undertake a systematic structure,activity relationship study of this cyclopeptide, based on the Ala-scan technique, in order to obtain useful information for the rational design of additional analogues. The synthesis and characterization of the seven Ala modified analogues are reported and their biological and pharmacological properties are described. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Low bandgap ,-conjugated copolymers based on fused thiophenes and benzothiadiazole: Synthesis and structure-property relationship studyJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 20 2009Shiming Zhang Abstract A series of low bandgap conjugated polymers consisting of benzothiadiazole alternating with dithienothiophene (DTT) or dithienopyrrole (DTP) unit with or without 3-alkylthiophene bridge have been synthesized. Effect of the fused rings and 3-alkylthiophene bridge on the thermal, optical, electrochemical, charge transport, and photovoltaic properties of these polymers have been investigated. These polymers show broad absorption extending from 300 to 1000 nm with optical bandgaps as low as 1.2 eV; the details of which can be varied either by incorporating 3-alkylthiophene bridge or by replacing DTT with DTP. The LUMO levels (,2.9 to ,3.3 eV) are essentially unaffected by the specific choice of donor moiety, whereas the HOMO levels (,4.6 to ,5.6 eV) are more sensitive to the choice of donor. The DTT and DTP polymers with 3-alkylthiophene bridge were found to exhibit hole mobilities of 8 × 10,5 and 3 × 10,2 cm2 V,1 s,1, respectively, in top-contact organic field-effect transistors. Power conversion efficiencies in the range 0.17,0.43% were obtained under simulated AM 1.5, 100 mW cm,2 irradiation for polymer solar cells using the DTT and DTP-based polymers with 3-alkylthiophene bridge as donor and fullerene derivatives as acceptor. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5498,5508, 2009 [source] Molecular Modeling Of The Aldose Reductase-Inhibitor Complex Based On The X-Ray Crystal Structure And Studies With Single-Site- Directed MutantsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2000S.B. Singh Aldose reductase (AR) has been implicated in the etiology of the secondary complications of diabetes. This enzyme catalyzes the reduction of glucose to sorbitol using nicotinamide adenine dinucleotide phosphate as an essential cofactor. AR has been localized at the sites of tissue damage, and inhibitors of this enzyme prevent the development of neuropathy, nephropathy, retinopathy, and cataract formation in animal models of diabetes. The crystal structure of AR complexed with zopolrestat, a potent inhibitor of AR, has been described. (1) We have generated a model of the AR-inhibitor complex based on the reported C alpha coordinates of the protein and results of a structure-activity relationship study using four structurally distinct classes of inhibitors, recombinant human AR, and four single-site-directed mutants of this enzyme. The effects of the site-directed mutations on residues within the active site of the enzyme were evaluated by average interaction energy calculations and by calculations of carbon atom surface area changes. These values correlated well with the IC50 values for zopolrestat with the wildtype and mutant enzymes, validating the model. On the basis of the zopolrestat-binding model, we have proposed binding models for 10 other AR inhibitors. Our models have enabled us to gain a qualitative understanding of the binding domains of the enzyme and how different inhibitors impact the size and shape of the binding site. [source] CP-MLR/PLS Directed Structure-Activity Modeling of the HIV-1 RT Inhibitory Activity of 2,3-Diaryl-1,3-thiazolidin-4-onesMOLECULAR INFORMATICS, Issue 4 2004Yenamandra Abstract A detailed structure-activity relationship study of the HIV-1 Reverse Transcriptase (RT) inhibitory activity of two series of compounds, 2-(2,6-dihalo phenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones and 2-(2,6-Dihalophenyl)-3-(substituted phenyl)-thiazolidin-4-ones, belonging to 2,3-diaryl-thiazolidin-4-ones in terms of physicochemical and structural descriptors have been carried out using combinatorial protocol interfaced multiple linear regression (CP-MLR) and partial least squares (PLS) analysis. The models developed in the study indicate a preference for hydrophobic compounds for better inhibitory activity. Also, a positive regression coefficient of I2,3, an indicator descriptor meant for the joint disposition of substituents of 2,3-diaryl moieties of thiazolidinones to address their ability in taking a butterfly like conformation, is in agreement with all earlier observations that compounds having the ability to take butterfly like conformation will be showing better inhibitory activity. The identified models suggest that the meta-positions of 3-aryl moiety has the ability to accommodate hydrophobic/ steric groups. The replacement of C2, of 3-phenyl by nitrogen resulted in 3-pyridyl variants of these analogues. Even though from geometry point of view, the phenyls and pyridyls span almost the same structural space and steric features, presence of nitrogen in pyridyls gave them a blend of polarity, electronic features and a different hydrophobicity profile when compared to corresponding phenyl analogue. Furthermore the PLS models, developed from those descriptors took part in CP-MLR models, indicate that most of the descriptors have almost equal influence in accounting for the variation in the activity of these compounds. This suggests that the factors responsible for the variation in the activity have been uniformly distributed across the varying centers of the molecule. The study suggests that thiazolidinones with 3-(pyridin-2-yl) moiety provide scope for further substituent variation to modulate the HIV-1 RT inhibitory activity. [source] Structure,activity relationship study of alkynyl ether insecticide synergists and the development of MB-599 (verbutin),PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 4 2003Béla Bertók Abstract Structure,activity relationships of aryl alkynyl synergists of the general formula of Ar,Q,R, where Q represents a bridging structure, were studied using a standardised testing system and Relative Potency values. Ethers, esters, oxime ethers, amides and amines were prepared and evaluated. The length of the R-alkynyl chain, the role of the bridge and the substitution of the aromatic ring were examined systematically. The most potent compounds possessed an aromatic ring connected via a bridge of three atoms to an alkynyl chain, forming together a linear side-chain of six atoms. Several highly potent compounds were synthesised of which one (MB-599; proposed common name verbutin) was selected for development as a selective insecticide synergist in crop protection. Its high potential at practical insecticide:synergist ratios makes possible the reduction of the total amount of insect-control chemicals applied, and its use as an additive to produce new formulations of existing insecticides makes it highly advantageous in resistance management, giving a new tool to sustain the effectiveness of a wide range of insecticides. A product containing a (1,+,1) mixture of verbutin and beta-cypermethrin was launched in Hungary in 2002. © 2003 Society of Chemical Industry [source] Lower Homologues of Okoumal and Disila-Okoumal: Synthesis and Olfactory Characterization of Novel Ambergris OdorantsCHEMBIOCHEM, Issue 3 2010Jennifer B. Nätscher A structure,odor relationship study on lower homologues of the ambergris odorant okoumal with an ElCH2El (3: El=C; 4: El=Si) or ElOEl moiety (5: El=Si) was carried out. All four stereoisomers of 3,5 were synthesized and characterized by odor descriptions and detection thresholds. The lowest odor thresholds were measured for the 2R configured isomers, with the 2R,4R configured 4,a (El=Si, X=CH2) being the most intense of the series and best also with respect to its odor character. [source] Exploring QSAR for Substituted 2-Sulfonyl-Phenyl-Indol Derivatives as Potent and Selective COX-2 Inhibitors Using Different Chemometrics ToolsCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2008Mehdi Khoshneviszadeh Selective inhibition of cyclooxygenase-2 inhibitors is an important strategy in designing of potent anti-inflammatory compounds with significantly reduced side effects. The present quantitative structure,activity relationship study, attempts to explore the structural and physicochemical requirements of 2-sulfonyl,phenyl,indol derivatives (n = 30) for COX-2 inhibitory activity using chemical, topological, geometrical, and quantum descriptors. Some statistical techniques like stepwise regression, multiple linear regression with factor analysis as the data preprocessing (FA-MLR), principal component regression analysis, and genetic algorithms partial least squares analysis were applied to derive the quantitative structure,activity relationship models. The generated equations were statistically validated using cross-validation and external test set. The quality of equations obtained from stepwise multiple linear regression, FA-MLR, principal component regression analysis and PLS were in the acceptable statistical range. The best multiple linear regression equation obtained from factor analysis (FA-MLR) as the preprocessing step could predict 77.5% of the variance of the cyclooxygenase-2 inhibitory activity whereas that derived from genetic algorithms partial least squares could predict 84.2% of variances. The results of quantitative structure,activity relationship models suggested the importance of lipophilicity, electronegativity, molecular area and steric parameters on the cyclooxygenase-2 inhibitory activity. [source] Structure,Activity Relationship Studies on Derivatives of Eudesmanolides from Inula helenium as Toxicants against Aedes aegypti Larvae and AdultsCHEMISTRY & BIODIVERSITY, Issue 7 2010Charles Abstract An Aedes aegypti larval toxicity bioassay was performed on compounds representing many classes of natural compounds including polyacetylenes, phytosterols, flavonoids, sesquiterpenoids, and triterpenoids. Among these compounds, two eudesmanolides, alantolactone, and isoalantolactone showed larvicidal activities against Ae. aegypti and, therefore, were chosen for further structure,activity relationship study. In this study, structural modifications were performed on both alantolactone and isoalantolactone in an effort to understand the functional groups necessary for maintaining and/or increasing its activity, and to possibly lead to more effective insect-control agents. All parent compounds and synthetic modification reaction products were evaluated for their toxic activities against Ae. aegypti larvae and adults. Structure modifications included epoxidations, reductions, catalytic hydrogenations, and Michael additions to the ,,, -unsaturated lactones. None of the synthetic isomers synthesized and screened against Ae. aegypti larvae were more active than isoalantolactone itself which had an LC50 value of 10.0,,g/ml. This was not the case for analogs of alantolactone for which many of the analogs had larvicidal activities ranging from 12.4 to 69.9,,g/ml. In general, activity trends observed from Ae. aegypti larval screening were not consistent with observations from adulticidal screening. The propylamine Michael addition analog of alantolactone was the most active adulticide synthesized with an LC50 value of 1.07,,g/mosquito. In addition, the crystal structures of both alantolactone and isoalantolactone were determined using CuK, radiation, which allowed their absolute configurations to be determined based on resonant scattering of the light atoms. [source] DNA Topoisomerase I Inhibitory Alkaloids from Corydalis saxicolaCHEMISTRY & BIODIVERSITY, Issue 7 2008Xuanxuan Cheng Abstract Chemical studies of the Chinese herb Corydalis saxicolaBunting led to the isolation and identification of 14 alkaloids, 1,14. Seven of these compounds, 4,9 and 11, were obtained from this plant for the first time. Feruloylagmatine (7) is the first guanidine-type alkaloid to be identified in the family Papaveraceae and in dicotyledonous plants. All of the isolated compounds were assayed for inhibitory activity against human DNA topoisomerase I. A DNA cleavage assay demonstrated that these alkaloids specifically inhibit topoisomerase through stabilization of the enzyme,DNA complex. Among the isolated alkaloids, (,)-pallidine (8) and (,)-scoulerine (11) showed strong inhibitory activities toward topoisomerase I that were comparable to camptothecin, a typical topoisomerase I inhibitor. A preliminary structure,activity relationship study suggested that the quaternary ammonium ion might play an important role in topoisomerase I inhibition by the isoquinoline alkaloids. These data indicated that DNA topoisomerase I inhibition represents probably one of the anticarcinogenic mechanisms of C. saxicola. [source] | ||||||||||