Search results for "Quantitative structure"

Discrete Derivatives for Atom-Pairs as a Novel Graph-Theoretical Invariant for Generating New Molecular Descriptors: Orthogonality, Interpretation an…

2013

This report presents a new mathematical method based on the concept of the derivative of a molecular graph (G) with respect to a given event (S) to codify chemical structure information. The derivate over each pair of atoms in the molecule is defined as ∂G/∂S(vi  , vj )=(fi -2fij +fj )/fij , where fi (or fj ) and fij are the individual frequency of atom i (or j) and the reciprocal frequency of the atoms i and j, respectively. These frequencies characterize the participation intensity of atom pairs in S. Here, the event space is composed of molecular sub-graphs which participate in the formation of the G skeleton that could be complete (representing all possible connected sub-graphs) or comp…

New antitrichomonal drug-like chemicals selected by bond (edge)-based TOMOCOMD-CARDD descriptors.

2008

Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental resu…

Provisional Classification and in Silico Study of Biopharmaceutical System Based on Caco-2 Cell Permeability and Dose Number

2013

Today, early characterization of drug properties by the Biopharmaceutics Classification System (BCS) has attracted significant attention in pharmaceutical discovery and development. In this direction, the present report provides a systematic study of the development of a BCS-based provisional classification (PBC) for a set of 322 oral drugs. This classification, based on the revised aqueous solubility and the apparent permeability across Caco-2 cell monolayers, displays a high correlation (overall 76%) with the provisional BCS classification published by World Health Organization (WHO). Current database contains 91 (28.3%) PBC class I drugs, 76 (23.6%) class II drugs, 97 (31.1%) class III d…

Biopartitioning micellar separation methods: modelling drug absorption

2003

The search for new pharmacologically active compounds in drug discovery programmes often neglects biopharmaceutical properties as drug absorption. As a result, poor biopharmaceutical characteristics constitute a major reason for the low success rate for candidates in clinical development. Since the cost of drug development is many times larger than the cost of drug discovery, predictive methodologies aiding the selection of bioavailable drug candidates are of profound significance. This paper has been focussed on recent developments and applications of chromatographic systems, particularly those systems based on amphiphilic structures, in the frame of alternative approaches for estimating t…

Supermolecular control of charge transfer in dye-sensitized nanocrystalline TiO2 films: towards a quantitative structure-function relationship.

2005

Chromatographic retention–activity relationships for prediction of the toxicity pH-dependence of phenols

2007

Abstract An investigation of the use of the chromatographic retention (log  k ) as an in vitro approach for modeling the pH-dependence of the toxicity to Guppy of phenols is developed. A data set of 19 phenols with available experimental toxicity–pH data was used. The importance of the mechanism of toxic action (MOA) of phenols was studied. log  k data at three pH values were used for the phenols classification and two groups or ‘MODEs’ were identified. For one ‘MODE’ a quantitative retention–activity relationship (QRAR) model was calculated. Finally, the model was used to assess the toxicity to Guppy of phenols at different pH values. The results of this investigation suggest that chromato…

A QSAR study investigating the potential anti-HIV-1 effect of some acyclovir and ganciclovir analogs

2009

A QSAR study, involving the use of calculated physical-chemical properties (TSAR TM ), and the use of a neural network approach (TSAR TM ), has been performed on the potential anti-HIV-1 activity of a series of Acyclovir and Ganciclovir analogs. Model obtained allows reliable predictions for the anti-HIV-1 activity of these derivatives, and showed that the presence of the Ganciclovir chain in triazolopyrrolopyrimidine and pyrimidopyrrolopyrimidine series seems to increase the antiviral effect.

3D-QSAR study of ligands for a human olfactory receptor

2005

Abstract Only about 350 olfactory receptors (OR) provide a basis for the remarkable ability of humans to recognise and discriminate a large number of odorants. A recent study reports the odorant repertoire of a human class II OR called OR1G1, including both agonists and antagonists. We used these affinity data to perform a 3D molecular modelling study of these ligands using Catalyst/HypoGen software (Catalyst v4.9.1, Accelrys Inc., San Diego, 2004) to propose alignment models for OR1G1 ligands. We obtained a triple-alignment model, which satisfactorily explained the experimental activities and was able both to predict the antagonist effects of some compounds and to identify new potent agoni…

Internal Test Sets Studies in a Group of Antimalarials

2006

Topological indices have been applied to build QSAR models for a set of 20 an- timalarial cyclic peroxy cetals. In order to evalua te the reliability of the proposed linear models leave-n-out and Internal Test Sets (ITS) approaches have b een considered. The pro- posed procedure resulted in a robust and consensued prediction equation and here it is shown why it is superior to the employed standard c ross-validation algorithms involving multilinear regression models.

Tracking Ca

2019

We characterize thus-far elusive domain rearrangements of a calcium-transporting ATPase in the native membrane.