摘要:

AbstractThe previously published model of the model‐based quantitative structure‐time‐activity relationship (QSTAR) for growth inhibitory activity of nonionizable series of kojic acid (5‐hydroxy‐2‐hydroxymethyl‐4H‐pyrane‐4‐one) derivatives againstEscherichia colihas been extended for the complete set consisting of 21 nonionizable and 14 ionizable compounds. The inhibitory activity has been characterized by the isoeffective concentrations causing 50%‐decrease in the specific growth rate in comparison with the untreated control after the five exposure periods in 7 media differing in theirpHvalues (pH5.6–8.0). For an acceptable fit of the model to the data the receptor binding of both ionized and nonionized molecules had to be considered and the model modified accordingly. The model describes the toxicity of the tested compounds as an explicit non‐linear function of hydro‐phobicity,pKa values, the size of the substituent in the position 2, thepHvalues of the external media, and the time of exposure. The results can be interpreted as follows. Elimination as well as binding to the receptor have been positively influenced by both size of the molecules and ionization. The ionized molecules exhibit about 2.6 × 103stronger binding to the receptors than their nonionized counterparts. The QSTAR model can be used for rational development o

ISSN:0931-8771    

DOI:10.1002/qsar.19970160402

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractModels investigating relationships between chemical structures and biological activities are receiving increased recognition for the identification of chemicals with the potential for inducing adverse health effects. The relationships can be either qualitative (noted as SAR) or quantitative (noted as QSAR). The objective of the present study was to define an effective process for evaluating such models. The predictivity of SAR/QSAR models derived from the U.S. National Toxicology Program Rodent Carcinogenicity Bioassay endeavor by CASE/MultiCASE was evaluated by several different approaches: leave‐one‐out tests, 10‐fold cross‐validations and by the use of an independent test set. The goodness‐of‐fit for the data used in the model building, the predictivity for the chemicals not contained in the model, and the consistency of the predictions for a group of chemicals by different SAR/QSAR sub‐models were examined systematically. Individual prediction indices generated by CASE/MultiCASE, arbitrary combinations thereof, as well as weighted combinations using Bayes' theorem, were utilized to derive predictions of Carcinogenicity. Combinations derived using Bayes' theorem provided the most predictive model. The closeness between sub‐models based on the leave‐one‐out procedure and the full model (all chemicals used for model building) makes it the most reliable process for the estimation of a model's predictivity. However, the similarity between the predictions of the leave‐one‐out models and the 10‐fold cross‐validation models indicates that the latter process prov

ISSN:0931-8771    

DOI:10.1002/qsar.19970160403

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractConventional parametric methods such as linear regression have not been entirely successful in analyzing structure‐activity data sets. This is because the underlying relationships may involve nonlinearities, thresholds and interactions, all of which considerably impede linear additive modelling approaches. Recursive partitioning, RP, is able to accommodate all these modelling difficulties seamlessly and therefore invites investigation as a general approach for study of structure activity relationships.In this paper we apply a recursive partitioning procedure, FIRM, to a large monoamine oxidase structure‐activity data set. The methodology is successful in uncovering nonlinearities in the response. Coupling RP with the use of correspondence analysis provides further insights into the distinction between compounds that are inactive, moderately active and act

ISSN:0931-8771    

DOI:10.1002/qsar.19970160404

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractThe description of field‐induction σ (σi) parameters in a Comparative Molecular Field Analysis has been previously attempted by incorporating electrostatic fields computed either from point charges or from electrostatic potentials. Also, σ as well as σihave been correlated for a series of groups (–X) with the lowest electrostatic potential around the nitrogen in a series of singly substituted (NH2– X) amines [6,7]. Here a correlation is established between both field‐induction and resonance σ (σiand σrrespectively) parameters for a series of groups (–X) and electron densities of molecules (R‐X) substituted with these groups, incorporated into a Comparative Molecular Field Analysis (CoMFA). The correlation has been established for a series of singly substituted amines (R=NH2‐) as well as para substituted benzoic acids (R=HOOC(p) ‐ C6H4‐) with the correlation coefficients being explained quite well. The crossvalidated r2(q2) as well as the predicted r2for a different series of groups have provided valid stress tests for the correlations. The electron densities for the various substituted amines are calculated using the AMI Ha

ISSN:0931-8771    

DOI:10.1002/qsar.19970160405

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

摘要:

AbstractA new molecular index is proposed that is derived from the eigenvalues of a modified adjacency matrix. The construction of the matrix is chemically intuitive in that its elements relate to atomic and bonding properties. The index was tested by comparing its performance in predicting the experimentalLogPof 230 compounds. The predictive power of the index is shown to be both superior than and complementary to traditional connectivity indices, χ, forLogP

ISSN:0931-8771    

DOI:10.1002/qsar.19970160406

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160407

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160408

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160409

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19970160401

出版商:WILEY‐VCH Verlag    

年代:1997

数据来源: WILEY