Search results for "Quantitative structure"
showing 10 items of 192 documents
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…
tomocomd-camps and protein bilinear indices - novel bio-macromolecular descriptors for protein research: I. Predicting protein stability effects of a…
2010
Descriptors calculated from a specific representation scheme encode only one part of the chemical information. For this reason, there is a need to construct novel graphical representations of proteins and novel protein descriptors that can provide new information about the structure of proteins. Here, a new set of protein descriptors based on computation of bilinear maps is presented. This novel approach to biomacromolecular design is relevant for QSPR studies on proteins. Protein bilinear indices are calculated from the kth power of nonstochastic and stochastic graph–theoretic electronic-contact matrices, and , respectively. That is to say, the kth nonstochastic and stochastic protein bili…
Atom-Based Quadratic Indices to Predict Aquatic Toxicity of Benzene Derivatives to <i>Tetrahymena pyriformis</i>
2009
The non-stochastic and stochastic atom-based quadratic indices are applied to develop quantitative structure-activity relationship (QSAR) models for the prediction of aquatic toxicity. The used dataset, consisting of 392 benzene derivatives for which toxicity data to the ciliate Tetrahymena pyriformis were available, is divided into training and test sets. The obtained multiple linear regression models are statistically significant (R2 = 0.787 and s = 0.347, R2 = 0.806 and s = 0.329, for non-stochastic and stochastic quadratic indices, respectively) and show rather good stability in a cross-validation experiment (q2 = 0.769 and scv = 0.357, q2 = 0.791 and scv = 0.337, correspondingly). In a…
Modeling the chiral resolution ability of highly sulfated β-cyclodextrin for basic compounds in electrokinetic chromatography
2013
Abstract Despite the fact that extensive research in the field of enantioseparations by capillary electrophoresis has been carried out, it is difficult to predict whether a concrete chiral selector would be useful for the separation of a racemic compound. Hence, several experimental effort is necessary to test the abilities of individual chiral selectors, usually by trial and error procedures. Thus, the enantioseparation of a new racemate becomes a time- and money-consuming task. In this work, the ability of highly sulfated β-cyclodextrin (HS-β-CD) as chiral selector in electrokinetic chromatography (EKC) is modeled for the first time, using exclusively directly-available structural data of…