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SAR and QSAR in Environmental Research

D T Manallack
Drug-likeness has long been studied in the pursuit of finding new medicines. Similarly, in the agrochemical field there is value in exploring the properties of the chemicals involved. Patterns that emerge can potentially influence future discovery campaigns to improve the probability of commercial success. In this study we investigate the acid/base properties and physicochemical characteristics of three classes of compounds: fungicides, herbicides and insecticides. In comparison with FDA-approved drugs, it was noted that the pesticides were generally smaller, possessed a neutral charge state and were more lipophilic...
August 11, 2017: SAR and QSAR in Environmental Research
K Khan, K Roy
In this study, externally validated quantitative structure-toxicity relationship (QSTR) models were developed for toxicity of cosmetic ingredients on three different ecotoxicologically relevant organisms, namely Pseudokirchneriella subcapitata, Daphnia magna and Pimephales promelas following the OECD guidelines. The final models were developed by partial least squares (PLS) regression technique, which is more robust than multiple linear regression. The obtained model for P. subcapitata shows that molecular size and complexity have significant impacts on the toxicity of cosmetics...
August 7, 2017: SAR and QSAR in Environmental Research
J C Dearden, M Hewitt, G M Bresnen, C N Gregg
Animal models are known not to predict human responses well, in general. However, we have been able to demonstrate that, for a series of non-steroidal anti-inflammatory drugs that are or were in clinical use, the incorporation of two simple physicochemical properties results in excellent correlations between human and rodent potencies for anti-inflammatory, analgesic and anti-pyretic activities. This has the potential to allow the use of historical data to improve drug development.
July 25, 2017: SAR and QSAR in Environmental Research
C R García-Jacas, Y Marrero-Ponce, T Hernández-Ortega, K Martinez-Mayorga, L Cabrera-Leyva, J C Ledesma-Romero, I Aguilera-Fernández, A R Rodríguez-León
A novel mathematical procedure to codify chiral features of organic molecules in the QuBiLS-MIDAS framework is introduced. This procedure constitutes a generalization to that commonly used to date, where the values 1 and -1 (correction factor) are employed to weight the molecular vectors when each atom is labelled as R (rectus) or S (sinister) according to the Cahn-Ingold-Prelog rules. Therefore, values in the range [Formula: see text] with steps equal to 0.25 may be accounted for. The atoms labelled R or S can have negative and positive values assigned (e...
July 14, 2017: SAR and QSAR in Environmental Research
S Önlü, M Türker Saçan
Quantitative structure-activity relationship (QSAR) modelling is a major tool employed in the prediction of various endpoints. However, current QSAR literature is missing a full understanding of the impact of quantum chemical calculation methods on the estimation of molecular descriptors and model performance. Here, we provide a comprehensive analysis of the quantitative effects of different geometry optimization methods (semi-empirical, ab initio Hartee-Fock and density functional theory) on the molecular descriptors...
July 14, 2017: SAR and QSAR in Environmental Research
T M Martin, C R Lilavois, M G Barron
Previous modelling of the median lethal dose (oral rat LD50) has indicated that local class-based models yield better correlations than global models. We evaluated the hypothesis that dividing the dataset by pesticidal mechanisms would improve prediction accuracy. A linear discriminant analysis (LDA) based-approach was utilized to assign indicators such as the pesticide target species, mode of action, or target species - mode of action combination. LDA models were able to predict these indicators with about 87% accuracy...
July 13, 2017: SAR and QSAR in Environmental Research
S Bitam, M Hamadache, S Hanini
A new family of AChE inhibitors, N-benzylpiperidines, showed exceptional efficacy in vitro and in vivo, minimal side effects and high selectivity for acetylcholinesterase (AChE). Three regression methods were chosen in this work to develop robust predictive models, namely multiple linear regression (MLR), genetic function approximation (GFA) and multilayer perceptron network (MLP). Ten descriptors were selected for a dataset of 99 molecules, using a genetic algorithm. The best results were obtained for MLP with a 10-6-1 artificial neural network model trained with the Broyden-Fletcher-Goldfarb-Shanno (BFGS) algorithm...
June 14, 2017: SAR and QSAR in Environmental Research
J P Doucet, E Papa, A Doucet-Panaye, J Devillers
QSAR models are proposed for predicting the toxicity of 33 piperidine derivatives against Aedes aegypti. From 2D topological descriptors, calculated with the PaDEL software, ordinary least squares multilinear regression (OLS-MLR) treatment from the QSARINS software and machine learning and related approaches including linear and radial support vector machine (SVM), projection pursuit regression (PPR), radial basis function neural network (RBFNN), general regression neural network (GRNN) and k-nearest neighbours (k-NN), led to four-variable models...
June 12, 2017: SAR and QSAR in Environmental Research
A Bak, V Kozik, A Smolinski, J Jampilek
Finding a balance between a desired drug's potency and its physicochemical properties that are important for its molecule pharmacokinetic or pharmacodynamics profile is still a challenging issue in rational drug discovery. Quantitative assessment of the lipophilic characteristics of potential drug molecules is indispensable for efficient development of Absorption, Distribution, Metabolism, Excretion, Toxicity-tailored structure-activity models; therefore reliable procedures for deriving log P from molecular structure are desirable...
June 2, 2017: SAR and QSAR in Environmental Research
D López-Malo, J I Bueso-Bordils, M J Duart, P A Alemán-López, R V Martín-Algarra, G M Antón-Fos, L Lahuerta-Zamora, J Martínez-Calatayud
Fluorimetric analysis is still a growing line of research in the determination of a wide range of organic compounds, including pharmaceuticals and pesticides, which makes necessary the development of new strategies aimed at improving the performance of fluorescence determinations as well as the sensitivity and, especially, the selectivity of the newly developed analytical methods. In this paper are presented applications of a useful and growing tool suitable for fostering and improving research in the analytical field...
July 2017: SAR and QSAR in Environmental Research
C Chen, D Wang, H Wang, Z Lin, Z Fang
Quorum sensing inhibitors (QSIs) are promising alternatives to antibiotics, but they are discharged into the environment after their use cycle. This poses joint effects on the organisms in the environment. Therefore, it is of great importance to study the combined toxicities of QSIs and antibiotics. In this study, we investigated the single and combined toxicities of four potential QSIs and 11 sulfonamides (SAs) on Escherichia coli. The results revealed that the single toxicities of SAs were greater than those of QSIs, and the toxicities were found positively related to the binding energies (Ebind) with their target proteins, for both antibiotics and QSIs...
July 2017: SAR and QSAR in Environmental Research
N H Dimitrova, I A Dermen, N D Todorova, K G Vasilev, S D Dimitrov, O G Mekenyan, Y Ikenaga, T Aoyagi, Y Zaitsu, C Hamaguchi
In Europe, REACH legislation encourages the use of alternative in silico methods such as (Q)SAR models. According to the recent progress of Chemical Substances Control Law (CSCL) in Japan, (Q)SAR predictions are also utilized as supporting evidence for the assessment of bioaccumulation potential of chemicals along with read across. Currently, the effective use of read across and QSARs is examined for other hazards, including biodegradability. This paper describes the results of external validation and improvement of CATALOGIC 301C model based on more than 1000 tested new chemical substances of the publication schedule under CSCL...
June 2017: SAR and QSAR in Environmental Research
M C A Costa, M M C Ferreira
A series of 50 derivatives of 1,4-naphthoquinone tested against human HL-60 leukaemic cells showed activity at a wide range of concentrations. A multivariate quantitative structure-activity relationship (QSAR) study of 45 compounds was performed through principal component analysis (PCA) and partial least squares (PLS) regression. A good PLS regression model was obtained with two factors describing 60.1% of the total variance, and the selected descriptors were partial atomic charge at carbons 1 and 10 (C1 and C10) and total dipole moment (DIP)...
May 11, 2017: SAR and QSAR in Environmental Research
R Geerts, C G van Ginkel, C M Plugge
The biodegradation of N-alkyl polypropylene polyamines (NAPPs) was studied using pure and mixed cultures to enable read-across of ready biodegradability test results. Two Pseudomonas spp. were isolated from activated sludge with N-oleyl alkyl propylene diamine and N-coco alkyl dipropylene triamine, respectively. Both strains utilized all NAPPs tested as the sole source of carbon, nitrogen and energy for growth. Mineralization of NAPPs was independent of the alkyl chain length and the size of the polyamine moiety...
May 8, 2017: SAR and QSAR in Environmental Research
O Martínez-Santiago, Y Marrero-Ponce, R Vivas-Reyes, O M Rivera-Borroto, E Hurtado, M A Treto-Suarez, Y Ramos, F Vergara-Murillo, M E Orozco-Ugarriza, Y Martínez-López
Graph derivative indices (GDIs) have recently been defined over N-atoms (N = 2, 3 and 4) simultaneously, which are based on the concept of derivatives in discrete mathematics (finite difference), metaphorical to the derivative concept in classical mathematical analysis. These molecular descriptors (MDs) codify topo-chemical and topo-structural information based on the concept of the derivative of a molecular graph with respect to a given event (S) over duplex, triplex and quadruplex relations of atoms (vertices)...
May 2017: SAR and QSAR in Environmental Research
R B Aher, K Roy
Current research on antimalarial protein kinases has provided an opportunity to design kinase-based antimalarial drugs. We have developed a common feature-based pharmacophore model from a set of multiple chemical scaffolds including derivatives of 3,6-imidazopyridazines, pyrazolo[2,3-d]pyrimidines and imidazo[1,5-a]pyrazines, in order to incorporate the maximum structural diversity information in the model for the Plasmodium falciparum calcium-dependent protein kinase-1 (PfCDPK-1) target. The best pharmacophore model (Hypo-1) with the essential features of two hydrogen bond donors (HBD), one hydrophobic aromatic (HYAr) and one ring aromatic (RA) showed the classification accuracies of 86...
May 2017: SAR and QSAR in Environmental Research
Z Y Algamal, M K Qasim, H T M Ali
Descriptor selection is a procedure widely used in chemometrics. The aim is to select the best subset of descriptors relevant to the quantitative structure-activity relationship (QSAR) study being considered. In this paper, a new descriptor selection method for the QSAR classification model is proposed by adding a new weight inside L1-norm. The experimental results from classifying the neuraminidase inhibitors of influenza A viruses (H1N1) demonstrate that the proposed method in the QSAR classification model performs effectively and competitively compared with other existing penalized methods in terms of classification performance and the number of selected descriptors...
May 2017: SAR and QSAR in Environmental Research
M Stasevych, V Zvarych, V Lunin, N G Deniz, Z Gokmen, O Akgun, E Ulukaya, V Poroikov, T Gloriozova, V Novikov
Anticancer activity as an associated action for a series of dithiocarbamates of 9,10-anthracenedione was predicted using the PASS computer program and analysed with PharmaExpert software. The predicted cytotoxic activity of the dithiocarbamate derivatives of 9,10-anthracenedione was evaluated in vitro on cancer cells of the human lung (A549), prostate (PC3), colon (HT29) and human breast (MCF7) using the sulforhodamine B (SRB) cell viability assay. Among these compounds, 9,10-dioxo-9,10-dihydroanthracen-1-yl pyrrolidin-1-carbodithioate and 9,10-dioxo-9,10-dihydroanthracen-2-yl pyrrolidin-1-carbodithioate were identified as the most potent anticancer agents with cytotoxic activity against the MCF-7 human breast cell line with GI50 values of 1...
May 2017: SAR and QSAR in Environmental Research
J M Fitzpatrick, G Patlewicz
The information characterizing key events in an Adverse Outcome Pathway (AOP) can be generated from in silico, in chemico, in vitro and in vivo approaches. Integration of this information and interpretation for decision making are known as integrated approaches to testing and assessment (IATA). One such IATA was published by Jaworska et al., which describes a Bayesian network model known as ITS-2. The current work evaluated the performance of ITS-2 using a stratified cross-validation approach. We also characterized the impact of replacing the most significant component of the network, output from the expert system TIMES-SS, with structural alert information from the OECD Toolbox and Toxtree...
April 20, 2017: SAR and QSAR in Environmental Research
M A Azam, J Thathan
DNA gyrase subunit B (GyrB) is an attractive drug target for the development of antibacterial agents with therapeutic potential. In the present study, computational studies based on pharmacophore modelling, atom-based QSAR, molecular docking, free binding energy calculation and dynamics simulation were performed on a series of pyridine-3-carboxamide-6-yl-urea derivatives. A pharmacophore model using 49 molecules revealed structural and chemical features necessary for these molecules to inhibit GyrB. The best fitted model AADDR...
April 12, 2017: SAR and QSAR in Environmental Research
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