摘要:

Thiobenzanilides are found to show strong biological activity as antimicrobial, antimycotic, and tuberculostatic agents. In addition, they are relatively weakly toxic to higher organisms.

ISSN:1062-936X    

DOI:10.1080/10629369908033221

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

The CASE/MULTICASE structure-activity relationship (SAR) system was used to assess a new procedure to investigate the mechanistic relatedness of various toxicological endpoints. The method consisted of predicting the activity of 10,000 randomly selected chemicals using validated and characterized SAR models from a variety of biological and toxicological endpoints. The prevalence of chemicals predicted to possess the ability to induce two or more toxicological effects simultaneously should provide a measure of the mechanistic relatedness of these phenomena. Eight toxicological endpoints were predicted and the results were compared to predictions based on an eye irritation SAR model. Allergic contact dermatitis demonstrated a 29.6% greater than expected overlap between expected and observed results (p< 0.001). Similar results were seen for respiratory hypersensitivity (33.1%), sensory irritation (28.9%), cell toxicity (25.9%), and Ah receptor binding (19.8%). A lesser degree of overlap was seen between eye irritation andSalmonellamutagenicity (11.5%) and the inhibition of gap junction intercellular communication (6.7%). Moreover, a negative overlap, suggesting possibly an antagonistic phenomena, was observed between eye irritation and α2μ-induced nephropathy. These results indicate that this method can provide a useful tool to investigate mechanistic relatedness between diverse toxicological endpoints.

ISSN:1062-936X    

DOI:10.1080/10629369908033222

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

In this paper molecular quantum similarity measures (MQSM) are used to describe molecular toxicity and to construct Quantitative Structure-Toxicity Relationships (QSTR) models. This study continues the recently described relationships between MQSM and logPvalues, which permits to use the theoretical MQSM as an alternative to the empirical hydrophobic parameter in QSPR studies. In addition a new type of MQSM is presented in this work: it is based on the expectation value of electron–electron repulsion energy. The molecular properties studied here, as application examples are aquatic toxicity, toxicology on Bacteria and inhibition of a macromolecule employing four different molecular sets.

ISSN:1062-936X    

DOI:10.1080/10629369908033223

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

Carboxylic acids have been conspicuously absent from the quantitative structure activity relationship (QSAR) literature. This study investigated the aquatic toxicity (log(IGC−150)) of selected mono- and di-carboxylic acids and their sodium, or disodium salts, tested in theTetrahymenapopulation growth assay. The relationship between log(IGC−150) and hydrophobicity as described by the 1-octanol/water partition coefficient (logKow) revealed a distinct sub-class. The relationship [log(IGC−150) = 0.27(logKow) – 0.68;n= 16,r2= 0.943.s= 0.07,F= 233, Pr>F= 0.0001] was derived for mono-carboxylic acids. The QSAR [log(IGC−150) = 0.19(logKow) – 0.66;n= 9,r2= 0.951,s= 0.08,f= 135, Pr <F= 0.0001] was generated for the di-carboxylic acids. Regression analysis of data for the monosodium carboxylic acid salts yielded the model, log(IGC−150) = 0.60 (logKow) + 0.58;n= 4,r2= 0.932,s= 0.19,F= 41.2, Pr <F= 0.008. Values for the ionization constant (pKa) and the energy of the lowest unoccupied molecular orbital (ELUMO) do not vary within the sub-class for saturated acids. Moreover,pKuandELUMOdid not describe differences in toxicity between sub-classes of saturated aliphatic carboxylic acids and salts. However, these descriptors did vary for unsaturated acids. Inclusion of unsaturated acids afforded the derivation of a global response-surface for all aliphatic carboxylic acids, log(IGC−150) = 0.25(logKow) – 0.13(ELUMO) – 0.54;n= 34,r2= 0.850,s= 0.138,F= 87.9, Pr <F= 0.0001. Outliers to the response-surface included small molecules that provided 2-positions in which the molecule could potentially undergo electrophilic attacked and other more large, hydrophobic molecules.

ISSN:1062-936X    

DOI:10.1080/10629369908033224

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor

摘要:

This is a scanned image of the original Editorial Board page(s) for this issue.

ISSN:1062-936X    

DOI:10.1080/10629369908033220

出版商:Taylor & Francis Group    

年代:1999

数据来源: Taylor