Search results for "Structure-Activity Relationship"
showing 10 items of 743 documents
Biopartitioning micellar chromatoraphy to predict blood to lung, blood to liver, blood to fat and blood to skin partition coefficients of drugs
2009
[EN] Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 in adequate experimental conditions, has demonstrated to be useful in mimicking the drug partitioning process into biological systems. In this paper, the usefulness of BMC for predicting the partition coefficients from blood to lung, blood to liver. blood to fat and blood to skin is demonstrated. PLS2 and multiple linear regression (MLR) models based on BMC retention data are proposed and compared with other ones reported in bibliography. The proposed models present better or similar descriptive and predictive capability. (C) 2008 Elsevier B.V. All rights r…
Quantitative structure-activity relationships for the toxicity of organophosphorus and carbamate pesticides to the Rainbow trout Onchorhyncus mykiss.
2006
This study has investigated the development of quantitative structure-activity relationships (QSARs) for the toxicity to rainbow trout Onchorhyncus mykiss Walbaum of 75 organophosphorus and carbamate pesticides. The toxicity data were obtained from an openly available toxicological database and were selected to be representative of a single endpoint. A large number of physicochemical and structural descriptors were calculated for the pesticides. QSAR models were developed using multiple linear regression and partial least-squares analyses. Following the removal of a small number of outliers, predictive QSARs were developed on small numbers of mechanistically relevant descriptors. Applying m…
Novel Cancer Chemotherapy Hits by Molecular Topology: Dual Akt and Beta-Catenin Inhibitors
2015
Background and purposeColorectal and prostate cancers are two of the most common types and cause of a high rate of deaths worldwide. Therefore, any strategy to stop or at least slacken the development and progression of malignant cells is an important therapeutic choice. The aim of the present work is the identification of novel cancer chemotherapy agents. Nowadays, many different drug discovery approaches are available, but this paper focuses on Molecular Topology, which has already demonstrated its extraordinary efficacy in this field, particularly in the identification of new hit and lead compounds against cancer. This methodology uses the graph theoretical formalism to numerically chara…
Use of Catalyst in a 3D-QSAR Study of the Interactions between Flavor Compounds and β-Lactoglobulin
2003
This paper reports a 3D-QSAR study using Catalyst software to explain the nature of interactions between flavor compounds and beta-lactoglobulin. A set of 35 compounds, for which dissociation constants were previously determined by affinity chromatography, was chosen. The set was divided into three subsets. An automated hypothesis generation, using HypoGen software, produced a model that made a valuable estimation of affinity and provided an explanation for the lack of correlation previously observed between the hydrophobicity of terpenes and the affinity for the protein. On the basis of these results, it appears that aroma binding to beta-lactoglobulin is caused by both hydrophobic interac…
Use of molecular topology for the prediction of physico-chemical, pharmacokinetic and toxicological properties of a group of antihistaminic drugs
2002
We used molecular connectivity to search mathematical models for predicting physico-chemical (e.g. the partition coefficient, P), pharmacokinetic (e.g. the time of maximum plasma level, and toxicological properties (lethal dose, LD) for a group of antihistaminic drugs. The results obtained clearly reveal the high efficiency of molecular topology for the prediction of these properties. Randomization and cross-validation by use of leave-one-out tests were also performed in order to assess the stability and the prediction ability of the connectivity functions selected.
Application of the modelling power approach to variable subset selection for GA-PLS QSAR models
2007
A previously developed function, the Modelling Power Plot, has been applied to QSARs developed using partial least squares (PLS) following variable selection from a genetic algorithm (GA). Modelling power (Mp) integrates the predictive and descriptive capabilities of a QSAR. With regard to QSARs for narcotic toxic potency, Mp was able to guide the optimal selection of variables using a GA. The results emphasise the importance of Mp to assess the success of the variable selection and that techniques such as PLS are more robust following variable selection.
Determination of the hydrophobicity of organic compounds measured as logPo/w through a new chromatographic method
2009
A new chromatographic method to determine the octanol-water partition coefficient (logP(o/w)) of organic substances is proposed in this paper. This method is based on a previously reported model that relates the retention factor in reversed-phase liquid chromatography with solute (p), mobile phase (P(m)(N)) and stationary phase (P(s)(N)) polarity parameters: logk=(logk)(0)+p(P(m)(N)-P(s)(N)). P(m)(N) values are calculated through expressions that depend only on the organic solvent fraction in the mobile phase. (logk)(0) and P(s)(N) parameters are characteristic of the chromatographic system and are determined from the retention of a selected set of 12 compounds. Then, the p value of a solut…
Opioid analgetics retention–pharmacologic activity models using biopartitioning micellar chromatography
2002
Opioids are drugs used in medicine for pain control. In this paper, retention-pharmacokinetics and retention-pharmacodynamics relationships of opioids are proposed and statistically validated. These models are based on the compound retention in the biopartitioning micellar chromatography system (BMC), a new methodology which has successfully been used to develop QRAR models for many other families of compounds. The obtained results are compared to the traditional QSAR models using lipophilicity data. The adequacy of QRAR models is due to the fact that the characteristics of the compounds such as the hydrophobicity, electronic charge and steric effects determine both their retention in BMC a…
QSPR prediction of chromatographic retention times of pesticides: Partition and fractal indices
2014
The high-performance liquid-chromatographic retentions of red-wine pesticide residues are modeled by structure-property relationships. The effect of different types of features is analyzed: geometric, lipophilic, etc. The properties are fractal dimensions, partition coefficient, etc., in linear and nonlinear correlation models. Biological plastic evolution is an evolutionary perspective conjugating the effect of acquired characters and relations that emerge among the principles of evolutionary indeterminacy, morphological determination and natural selection. It is applied to design the co-ordination index that is used to characterize pesticide retentions. The parameters used to calculate th…
Modelling bioconcentration of pesticides in fish using biopartitioning micellar chromatography.
2005
Ecotoxicity assessment is essential before placing new chemical substances on the market. An investigation of the use of the chromatographic retention (log k) in biopartitioning micellar chromatography (BMC) as an in vitro approach to evaluate the bioconcentration factor (BCF) of pesticides in fish is proposed. A heterogeneous set of 85 pesticides from six chemical families was used. For pesticides exhibiting bioconcentration in fish (experimental log BCF > 2), a quantitative retention-activity relationships (QRAR) model is able to perform precise log BCF estimations of new pesticides. Considering the present data, the results based on log k seem to be more reliable than those from availabl…