摘要:

AbstractIn the present paper we make a comparison among three different semi‐empirical methods (AMI, MNDO and PM3) for the optimization of the geometries and calculation of different properties of MX compounds. The results were used to develop a CoMFA model to correlate the TA100 mutagenicity of these compounds with the LUMO field. The correlations between the LUMO field and steric, electrostatic and CoMFA fields generated automatically by the SYBYL CoMFA program, were explored. A comparison among different values of grid spacing for the lattice and standard deviation thresholds for column filtering was carried out to select the best values for this and future work.The results indicate that AM1 and PM3 methods represent a real improvement over MNDO in respect to QSAR studies relating electronic properties and mutagenicity for these compound

ISSN:0931-8771    

DOI:10.1002/qsar.19960150302

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractHydrophobic interactions sometimes play an important role in enzymatic reactions. In order to interpret such reaction data on the basis of comparative molecular field analysis (CoMFA) some method of introducing lipophilic parameters is necessary, since in the conventional CoMFA approach only electrostatic and steric fields are included in the original version. In the present study, the idea of Molecular Lipophilicity Potential (MLP) was introduced into the original CoMFA algorithm and the glycine conjugation reactions were analyzed. The conjugation data used were the whole reaction of glycine conjugation as well as the initial step of the reaction where substrates bind to coenzyme CoA. The substrates used include aromatic as well as aliphatic carboxylic acids. The CoMFA approach can explain data of aromatic and aliphatic carboxylic acids with a single model, whereas the multiple linear regression (MLR) analysis affords separated results for these two kinds of carboxylic acids. Thus, wide applicability of the CoMFA approach is supported and the aromatic and aliphatic carboxylic acids are suggested to behave in a common fashion in the conjugation reaction of the first process.

ISSN:0931-8771    

DOI:10.1002/qsar.19960150303

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractMolecular topology has been applied to the design of new analgesic drugs, utilizing linear discriminant analysis and connectivity functions using different topological descriptors. Of a total of 26 compounds selected, 17 showed analgesic activity. The following stood out particularly, showing analgesic values greater than 75% regarding ASA (acetylsalicylic acid), the reference drug: 2‐(1‐propenyl)phenol, 2′4′ dimethylacetophenone, p‐chlorobenzohydrazide, 1‐(p‐chlorophenyl) propanol and 4‐benzoyl‐3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one. The usefulness of the design method has been demonstrated in the search of new chemical structures having analgesic effects, some of

ISSN:0931-8771    

DOI:10.1002/qsar.19960150304

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractThe toxicity of a number of non‐ionic surfactants towardsThamnocephalus platyurus(sweet water fairy shrimp) has been examined. The measurements have been performed with the use of so‐called Toxkits, and the results have been expressed both as a mean LC50value for each of the surfactants, and with a relative scale estimated using of multi dimensional scaling (MDS). An algorithm is shown in matlab code, with which it is possible to perform MDS on a difference matrix with a lot of systematically missing values. The thus obtained results have been combined with the physico‐chemical data for the surfactants, and QSAR models have been estimated for the toxicity (log(LC50)) of the surfactants. The physico‐chemical properties with the main influence on the models were the hydrophilic‐lipophilic‐balance (HLB), the hydrophobicity (log P), the critical micellar concentration (CMC) and the number of carbon atoms in the hydrophobic part (C) of the

ISSN:0931-8771    

DOI:10.1002/qsar.19960150305

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractThe antiinflammatory mechanism of phenols as radical scavengers was analyzed. The biradical formation process Ph‐OH → Ph‐O + H was studied by the reaction coordinate method using the semiempirical AM1 quantum‐mechanical method. The enthalpies of formation of ground, transition, and radical states were determined; other parameters like the reaction, stabilization and activation enthalpies for phenoxyl radical formation of fifteen phenolic compounds were also calculated and correlated with their antiinflammatory activities.The results suggest that the ability of phenols to form the phenoxyl radical and the stability of this derived radical are important in the antiinflammatory activities of phenolsvianeutralization of harmful r

ISSN:0931-8771    

DOI:10.1002/qsar.19960150306

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractAllergic contact dermatitis (ACD) is a widespread concern in which sensitization occurs to low molecular weight chemicals. Currently, animal and human assays are used to identify chemicals with potential to cause ACD. MultiCASE, a computer based structure‐activity relational system was employed to evaluate a data base of contact sensitizers and identify structural determinants (biophores) associated with sensitization. The data base was derived from reports of animal and human studies and consisted of 1034 chemicals of which 317 were classified as sensitizers (extreme, strong, moderate, or weak), 22 chemicals had marginal (questionable) activity, and 695 were inactive. MultiCASE identified 49 biophores with related expanded fragments which accounted for the activity of all active chemicals. The major biophores consisted of: 1) a nitrogen double‐bonded to a carbon or a nitrogen; 2) substituted aromatic structures; 3) thiol and disulfide containing fragments; and 4) electrophilic moieties. Modulators of each biophore, which either augmented or decreased potency, included additional structural fragments, two dimensional distance descriptors, as well as physico‐chemical characteristics. Internal evaluation of the data base indicated the sensitivity was 99.6%, and the specificity of the data set was 99.4%. Prediction of the activity of chemicals not in the learning set gave a concordance of 90.2% with experimental results. These findings demonstrate the ability of MultiCASE to identify contact sensitizers and suggest its ability to screen chemicals for their potential to produc

ISSN:0931-8771    

DOI:10.1002/qsar.19960150307

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19960150308

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19960150309

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19960150301

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY