Search results for "quantitative"
showing 10 items of 2409 documents
Similarity boosted quantitative structure-activity relationship--a systematic study of enhancing structural descriptors by molecular similarity.
2013
The concept of molecular similarity is one of the most central in the fields of predictive toxicology and quantitative structure-activity relationship (QSAR) research. Many toxicological responses result from a multimechanistic process and, consequently, structural diversity among the active compounds is likely. Combining this knowledge, we introduce similarity boosted QSAR modeling, where we calculate molecular descriptors using similarities with respect to representative reference compounds to aid a statistical learning algorithm in distinguishing between different structural classes. We present three approaches for the selection of reference compounds, one by literature search and two by…
Classification of Congeneric and QSAR of Homologous Antileukemic S–Alkylcysteine Ketones
2021
Based on a set of six vector properties, the partial correlation diagram is calculated for a set of 28 S-alkylcysteine diazomethyl- and chloromethyl-ketone derivatives. Those with the greatest antileukemic activity in the same class correspond to high partial correlations. A periodic classification is performed based on information entropy. The first four characteristics denote the group, and the last two indicate the period. Compounds in the same period and, especially, group present similar properties. The most active substances are situated at the bottom right. Nine classes are distinguished. The principal component analysis of the homologous compounds shows five subclasses included in t…
Extended GT-STAF information indices based on Markov approximation models
2013
Abstract A series of novel information theory-based molecular parameters derived from the insight of a molecular structure as a chemical communication system were recently presented and usefully employed in QSAR/QSPRs (J. Comp. Chem, 2013, 34, 259; SAR and QSAR in Environ. Res. 2013, 24). This approach permitted the application of Shannon’s source and channel coding entropic measures to a chemical information source comprised of molecular ‘fragments’, using the zero-order Markov approximation model (atom-based approach). This report covers the theoretical aspects of the extensions of this approach to higher-order models, introducing the first, second and generalized-order Markov approximati…
New hypoglycaemic agents selected by molecular topology.
2003
Abstract New compounds showing hypoglycaemic activity have been designed through a computer aided method based on quantitative structure–activity relationship (QSAR) and molecular connectivity. After calculation of topological indices for a set of 89 compounds including active and inactive with regards to hypoglycaemic action, linear discriminant analysis was performed so that a useful model to predict such an activity was achieved. Later on, the discriminant model was applied on a huge database so that fourteen compounds were selected as potential new hypoglycaemics. From them, just five were finally selected for experimental test on expected hypoglycaemic activity. Among the selected comp…
A topological substructural approach for the prediction of P-glycoprotein substrates
2006
A topological substructural molecular design approach (TOPS-MODE) has been used to predict whether a given compound is a P-glycoprotein (P-gp) substrate or not. A linear discriminant model was developed to classify a data set of 163 compounds as substrates or nonsubstrates (91 substrates and 72 nonsubstrates). The final model fit the data with sensitivity of 82.42% and specificity of 79.17%, for a final accuracy of 80.98%. The model was validated through the use of an external validation set (40 compounds, 22 substrates and 18 nonsubstrates) with a 77.50% of prediction accuracy; fivefold full cross-validation (removing 40 compounds in each cycle, 80.50% of good prediction) and the predictio…
Unified Markov thermodynamics based on stochastic forms to classify drugs considering molecular structure, partition system, and biological species:
2005
Abstract To date, molecular descriptors do not commonly account for important information beyond chemical structure. The present work, attempts to extend, in this sense, the stochastic molecular descriptors (Gonzalez-Diaz, H. et al., J. Mol. Mod. 2002, 8, 237), incorporating information about the specific biphasic partition system, the biological species, and chemical structure inside the molecular descriptors. Consequently, MARCH-INSIDE molecular descriptors may be identified with time-dependent thermodynamic parameters (entropy and mean free energy) of partition process. A classification function was developed to classify data of 423 drugs and up to 14 different partition systems at the s…
New tyrosinase inhibitors selected by atomic linear indices-based classification models.
2005
In the present report, the use of the atom-based linear indices for finding functions that discriminate between the tyrosinase inhibitor compounds and inactive ones is presented. In this sense, discriminant models were applied and globally good classifications of 93.51% and 92.46% were observed for non-stochastic and stochastic linear indices best models, respectively, in the training set. The external prediction sets had accuracies of 91.67% and 89.44%. In addition, these fitted models were used in the screening of new cycloartane compounds isolated from herbal plants. A good behavior is shown between the theoretical and experimental results. These results provide a tool that can be used i…
Aplicación de la topología molecular a la predicción de la actividad antimalárica de análogos de la 4-anilinoquinolina
2021
La malaria es una enfermedad parasitaria causada por protozoos del género Plasmodium y transmitida por vectores del género Anopheles . En 2019 esta enfermedad se cobró la vida de más de 400.000 personas, de las cuales un 94 % se concentraban en la región de África. Uno de los principales problemas en el control de la malaria es la aparición de resistencias frente a los diferentes fármacos que existen, es por ello que es necesario el desarrollo de alternativas antimaláricas eficaces. En este estudio se ha aplicado la topología molecular a una serie de compuestos análogos de la 4-anilinoquinolina con actividad inhibitoria de la proliferación de 3 cepas de Plasmodium falciparum, una sensibl…
Combined use of PCA and QSAR/QSPR to predict the drugs mechanism of action. An application to the NCI ACAM Database
2009
During the years the National Cancer Institute (NCI) accumulated an enormous amount of information through the application of a complex protocol of drugs screening involving several tumor cell lines, grouped into panels according to the disease class. The Anti-cancer Agent Mechanism (ACAM) database is a set of 122 compounds with anti-cancer activity and a reasonably well known mechanism of action, for which are available drug screening data that measure their ability to inhibit growth of a panel of 60 human tumor lines, explicitly designed as a training set for neural network and multivariate analysis. The aim of this work is to adapt a methodology (previously developed for the analysis of …
Molecular modelling and QSAR in the discovery of HIV-1 integrase inhibitors
2007
The treatment regimens for the HIV-1 have mainly included reverse transcriptase or protease inhibitors but their long-term clinical utility is limited by severe side effects and viral drug resistance. A new attractive target for chemotherapeutic intervention can be the Integrase enzyme, that mediates the integration of HIV-1 DNA into a host chromosome, for which there is no known counterparts in the host cell. A number of derivatives have been found to inhibit IN in in vitro assays, but no successful drug based on them has emerged so far, although many compounds have been proposed. Moreover most of the inhibitors do not belong to a very precise structural class: this fact makes these compou…