Quantitative Structure-activity Relationships最新文献_第4页

Impact of Orthogonal Signal Correction (OSC) on the Predictive Ability of CoMFA Models for the Ciliate Toxicity of Nitrobenzenes Dedicated to Professor Werner Klein, Schmallenberg (Germany), on the oaccastion of his 65th birthday 正交信号校正(OSC)对CoMFA模型对硝基苯的虫毒性预测能力的影响——献给Schmallenberg(德国)Werner Klein教授65岁生日之际

Quantitative Structure-activity Relationships Pub Date : 2002-05-01 DOI: 10.1002/1521-3838(200205)21:1<3::aid-qsar3>3.0.co;2-d

M. Bohác, Björn Loeprecht, J. Damborský, G. Schüürmann

引用次数: 17

Multivariate Discrimination between Modes of Toxic Action of Phenols 酚类物质毒性作用方式的多变量判别

Quantitative Structure-activity Relationships Pub Date : 2002-05-01 DOI: 10.1002/1521-3838(200205)21:1<12::AID-QSAR12>3.0.CO;2-M

A. Aptula, T. Netzeva, I. Valkova, M. Cronin, T. Schultz, R. Kühne, G. Schüürmann

{"title":"Multivariate Discrimination between Modes of Toxic Action of Phenols","authors":"A. Aptula, T. Netzeva, I. Valkova, M. Cronin, T. Schultz, R. Kühne, G. Schüürmann","doi":"10.1002/1521-3838(200205)21:1<12::AID-QSAR12>3.0.CO;2-M","DOIUrl":"https://doi.org/10.1002/1521-3838(200205)21:1<12::AID-QSAR12>3.0.CO;2-M","url":null,"abstract":"A set of 221 phenols, for which toxicity data to the ciliate Tetrahymena pyriformis were available, was subjected to stepwise linear discriminant analysis (LDA) in order to classify their toxic mechanisms of action. The compounds were a priori grouped into the following four mechanisms according to structural rules: polar narcotics, weak acid respiratory uncouplers, pro-electrophiles and soft electrophiles. Hydrophobicity with and without correction for ionisation (log K o w , log D o w u), acidity constant (pK a ), frontier orbital energies (E L U M O , E H O M O ) and hydrogenbond donor and acceptor counts were used as molecular descriptors. LDA models employing 3-6 variables achieved 86-89% overall correct classification of the four mechanisms, with more varied performance for respiratory uncouplers and pro-electrophiles. For the latter, a separate model was developed that discriminated compounds undergoing metabolic activation from compounds with different mechanisms very accurately. Model validation was performed by evaluating the simulated external prediction through LDA models built from complementary subsets.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"8 1","pages":"12-22"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72812162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 101

A Novel Approach for Prediction of Intestinal Absorption of Drugs in Humans based on Hydrogen Bond Descriptors and Structural Similarity 一种基于氢键描述符和结构相似性预测人类肠道药物吸收的新方法

Quantitative Structure-activity Relationships Pub Date : 2001-12-01 DOI: 10.1002/1521-3838(200112)20:5/6<402::AID-QSAR402>3.0.CO;2-6

O. Raevsky, K. Schaper, P. Artursson, J. McFarland

{"title":"A Novel Approach for Prediction of Intestinal Absorption of Drugs in Humans based on Hydrogen Bond Descriptors and Structural Similarity","authors":"O. Raevsky, K. Schaper, P. Artursson, J. McFarland","doi":"10.1002/1521-3838(200112)20:5/6<402::AID-QSAR402>3.0.CO;2-6","DOIUrl":"https://doi.org/10.1002/1521-3838(200112)20:5/6<402::AID-QSAR402>3.0.CO;2-6","url":null,"abstract":"A new approach to predict the intestinal absorption of drugs in humans is presented. It is based on structural similarity and hydrogen bonding properties (ΣC values) of drug-like compounds. The relationship between gastrointestinal absorption in humans and hydrogen bond descriptors for 100 structurally diverse drugs was studied. From the sigmoid relationship for passively transported drugs it could be concluded that those with ΣC values less than 14 were completely absorbed, whereas those with ΣC values higher than 18 were poorly absorbed. In cases where other transport mechanisms prevail due to special structural features, an absorption threshold can be significantly different. So, instead of including the whole set of compounds in the QSAR analyses, small subsets of 1 to 5 structurally related drugs (nearest neighbors of a drug of interest) estimated by means of similarity calculations were considered. The contribution of the passive transport component and the corresponding influence of hydrogen bond factors on absorption was assumed to be similar within the postulated subsets.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"24 1","pages":"402-413"},"PeriodicalIF":0.0,"publicationDate":"2001-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81820105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

Three‐Dimensional Quantitative Structure‐Activity Relationship of Arylalkylamine N‐acetyltransferase (AANAT) Inhibitors: A Comparative Molecular Field Analysis 芳基烷基胺N -乙酰转移酶(AANAT)抑制剂的三维定量结构-活性关系:比较分子场分析

Quantitative Structure-activity Relationships Pub Date : 2001-12-01 DOI: 10.1002/1521-3838(200112)20:5/6<414::AID-QSAR414>3.0.CO;2-V

P. Chavatte, S. Yous, N. Beaurain, C. Mesangeau, G. Ferry, D. Lesieur

引用次数: 4

Application of the Rough Set Theory in Structure Activity Relationships of Antielectrostatic Imidazolium Compounds 粗糙集理论在抗静电咪唑类化合物结构活性关系中的应用

Quantitative Structure-activity Relationships Pub Date : 2001-12-01 DOI: 10.1002/1521-3838(200112)20:5/6<395::AID-QSAR395>3.0.CO;2-#

J. Krysiński, A. Skrzypczak, G. Demski, B. Predki

引用次数: 6

Transformation of a Free-Wilson Matrix into Fourier Coefficients 自由-威尔逊矩阵到傅里叶系数的变换

Quantitative Structure-activity Relationships Pub Date : 2001-12-01 DOI: 10.1002/1521-3838(200112)20:5/6<422::AID-QSAR422>3.0.CO;2-Z

M. Holǐk, J. Halámek

引用次数: 4

Relationships between Hydrophobicity and Algistatic Activity of 5‐Aryl‐3H‐[1,3,4]oxadiazole‐2‐thiones 5 -芳基- 3H -[1,3,4]恶二唑- 2 -硫酮疏水性与抑藻活性的关系

Quantitative Structure-activity Relationships Pub Date : 2001-11-01 DOI: 10.1002/1521-3838(200111)20:4<291::AID-QSAR291>3.0.CO;2-Q

T. Schelenz, J. Klunker, T. Bernhardt, W. Schäfer, J. Dost

{"title":"Relationships between Hydrophobicity and Algistatic Activity of 5‐Aryl‐3H‐[1,3,4]oxadiazole‐2‐thiones","authors":"T. Schelenz, J. Klunker, T. Bernhardt, W. Schäfer, J. Dost","doi":"10.1002/1521-3838(200111)20:4<291::AID-QSAR291>3.0.CO;2-Q","DOIUrl":"https://doi.org/10.1002/1521-3838(200111)20:4<291::AID-QSAR291>3.0.CO;2-Q","url":null,"abstract":"A series of 10 acidic 5-aryl-3H-[1,3,4]oxadiazole-2-thiones was synthesized and characterized with regard to hydrophobic and algistatic properties. \u0000 \u0000 \u0000 \u0000Apparent octan-1-ol/water (buffer pH=7.41) partition coefficients (logPapp) were determined by the shake-flask method and used to calculate the partition coefficients of the un-ionized molecules (logPu) on the basis of known pKa values. Relationships between both sets of logP and hydrophobic substituent constants are reported. \u0000 \u0000 \u0000 \u0000Biological activity parameters (logA) were derived from growth tests using autotrophic Chlorella vulgaris cultures. The obtained data sets of logA and logP were used in QSAR studies. In this way it could be shown that the algistatic activity of meta- and para-substituted 5-aryl-3H-[1,3,4]-oxadiazole-2-thiones strongly correlates with logPapp, but slightly poorer with logPu. \u0000 \u0000 \u0000 \u0000The results are discussed and compared with analogous QSAR/QSPR found for earlier studied series of five-membered N-heterocycles (2-amino-5-aryl-[1,3,4]oxadiazoles, 4-aryl-5-alkyl-2,4-dihydro-[1,2,4]triazol-3-ones, 5-amino-1-aryl-1H-tetrazoles).","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"91 1","pages":"291-297"},"PeriodicalIF":0.0,"publicationDate":"2001-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85542153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

QSAR of Antimalarial Cyclic Peroxy Ketals II: Exploration of Pharmacophoric Site Using AM1 Calculations 抗疟环过氧酮的QSAR II:利用AM1计算探索药效位点

Quantitative Structure-activity Relationships Pub Date : 2001-11-01 DOI: 10.1002/1521-3838(200111)20:4<319::AID-QSAR319>3.0.CO;2-M

K. Roy, A. De, C. Sengupta

{"title":"QSAR of Antimalarial Cyclic Peroxy Ketals II: Exploration of Pharmacophoric Site Using AM1 Calculations","authors":"K. Roy, A. De, C. Sengupta","doi":"10.1002/1521-3838(200111)20:4<319::AID-QSAR319>3.0.CO;2-M","DOIUrl":"https://doi.org/10.1002/1521-3838(200111)20:4<319::AID-QSAR319>3.0.CO;2-M","url":null,"abstract":"A series of antimalarial cyclic peroxy ketals (n=20) have been subjected to energy minimization using AM1 method, and Wang–Ford charges of the non-hydrogen common atoms (Figure 1), obtained from molecular electrostatic potential surface of the energy minimized geometries, have been used to model the antimalarial activity against P. falciparum. It is found that the difference in charges between the peroxy oxygens contribute positively to the activity, and this is in good agreement with the mode of antimalarial action of the peroxy compounds involving breakage of the peroxy bridge by the haem-iron within the parasite. It is hypothesized that difference in charges between two peroxy oxygens may facilitate the bond breakage. It is further found that the activity increases with increase in negative charge of the methoxy carbon of the common fragment of the molecule. This is related with possible secondary electronic interaction with the positively charged side chains of the histidine rich protein of P. falciparum. Attempt was made to incorporate steric and indicator parameters which emerged as important contributors from previous Hansch analysis. The present results support the previous observations that bulky phenyl ring substituents and a seven-member carbocylic ring attached to the peroxy bridge-containing ring are conducive to the activity.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"13 1","pages":"319-326"},"PeriodicalIF":0.0,"publicationDate":"2001-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85366290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Pharmacophore identification and bioactivity prediction for group I metabotropic glutamate receptor agonists by the electron-conformational QSAR method 电子构象QSAR法鉴定I类代谢性谷氨酸受体激动剂的药效团及生物活性预测

Quantitative Structure-activity Relationships Pub Date : 2001-11-01 DOI: 10.1002/1521-3838(200111)20:4<327::AID-QSAR327>3.0.CO;2-Q

E. Rosines, I. Bersuker, J. E. Boggs

{"title":"Pharmacophore identification and bioactivity prediction for group I metabotropic glutamate receptor agonists by the electron-conformational QSAR method","authors":"E. Rosines, I. Bersuker, J. E. Boggs","doi":"10.1002/1521-3838(200111)20:4<327::AID-QSAR327>3.0.CO;2-Q","DOIUrl":"https://doi.org/10.1002/1521-3838(200111)20:4<327::AID-QSAR327>3.0.CO;2-Q","url":null,"abstract":"The pharmacophore for group I metabotropic glutamate receptor (mGluRl) agonists is revealed and their activity predicted by means of the previously developed and further improved electron-conformational (EC) method. A distinguishing feature of this method is that in addition to revealing the pharmacophore of activity as a set of specific atomic electronic features arranged in a special geometry, it allows for prediction of the activity quantitatively as a function of the parameters of pharmacophore flexibility and anti-pharmacophore shielding groups. Conformational analysis, electronic structure calculations, and matrix processing are performed for the training set of 29 compounds, 13 active and 16 inactive, and the pharmacophore of mGluRl agonists is evaluated. It contains a four-point skeleton of three oxygen atoms and one nitrogen atom at certain interatomic distances with restricted atomic interaction indices whereby all these parameters are determined within certain tolerances. The pharmacophore parameter flexibilities, as well as the influence of the anti-pharmacophore shielding and other auxiliary groups are parameterized and weighted by seven constants, their values being obtained from a least-square regression with very good statistics: R 2 =0.97, F=589 (∼100% level of confidence), and a standard error of about 5% of the range of measured values. The results are also tested with the leave-one-out cross-validation method that yields prediction statistics R 2 = 0.91. The E statistics were also evaluated illustrating the role of each of the activity parameters involved.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"13 1","pages":"327-334"},"PeriodicalIF":0.0,"publicationDate":"2001-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85959270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

QSAR Modeling of Antimycobacterial Activity and Activity Against Other Bacteria of 3‐Formyl Rifamycin SV Derivatives 3‐甲酰基利福霉素SV衍生物抗细菌活性和抗其他细菌活性的QSAR模型

Quantitative Structure-activity Relationships Pub Date : 2001-11-01 DOI: 10.1002/1521-3838(200111)20:4<298::AID-QSAR298>3.0.CO;2-Z

I. DimovDimcho, Z. Nedyalkova, Svetla Haladjova, G. Schüürmann, O. Mekenyan

{"title":"QSAR Modeling of Antimycobacterial Activity and Activity Against Other Bacteria of 3‐Formyl Rifamycin SV Derivatives","authors":"I. DimovDimcho, Z. Nedyalkova, Svetla Haladjova, G. Schüürmann, O. Mekenyan","doi":"10.1002/1521-3838(200111)20:4<298::AID-QSAR298>3.0.CO;2-Z","DOIUrl":"https://doi.org/10.1002/1521-3838(200111)20:4<298::AID-QSAR298>3.0.CO;2-Z","url":null,"abstract":"Rifamycins form a class of antibiotics with a specific potency as drug against tuberculosis via inhibition of the DNA-dependent RNA polymerase. In the present study, literature data on the antibacterial potency against Mycobacterium tuberculosis and other bacteria of 53 derivatives of 3-formyl rifamycin SV are subjected to a QSAR analysis using AM1-based quantum chemical descriptors and the recently introduced dynamic approach that allows explicit consideration of the conformational space of properly generated 3D structures. Data pre-treatment includes normalization of the minimum inhibition concentration (MIC) values of ordinary bacteria using the well-known antituberculosis drug rifampicine as reference compound (RIA), and averaging over the different strains as motivated by a mathematical analysis of the two-step inhibition process. For both this generalized potency against ordinary bacteria and the antimycobacterial activity, QSAR modelling yields 3-variable regression equations with acceptable statistics for screening purposes (r2 around 0.60), which however differ partly in the stepwise-selected molecular descriptors and the respective conformers. While both types of activity are increased by increasing HOMO energy reflecting an increased electron donor capability and tendency to undergo hydroquinone-semiquinone-quinone oxidation, the models differ in the best 2nd and 3rd local quantum chemical descriptors, pointing to partially conflicting electronic structure requirements for optimal antimycobacterial activity and generalized activity against other bacteria. The discussion includes a detailed mechanistic analysis of the underlying bioreactivity aspects.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"2013 1","pages":"298-318"},"PeriodicalIF":0.0,"publicationDate":"2001-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87723635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8