Search results for "Quantitative structure"
showing 10 items of 192 documents
Quantitative structure-retention relationships for ionic and non-ionic compounds in biopartitioning micellar chromatography
2004
Quantitative structure–retention relationships, QSRRs, represent a powerful tool in chromatography. The objectives of QSRR studies are to predict the chromatographic retention behaviour of solutes based on their structural properties, to elucidate retention mechanisms, to optimize the separation of complex mixtures or to prepare experimental designs. In this paper, using the retention factors of 151 structurally unrelated solutes that cover a wide range of hydrophobicity, molecular size, hydrogen bonding properties and ionization degrees obtained in biopartitioning micellar chromatography (BMC) at different Brij35 micellar concentrations, several multivariate QSRR models are tested. It is d…
QRAR models for central nervous system drugs using biopartitioning micellar chromatography.
2002
The capability of biopartitioning Micellar Chromatography, BMC, to describe and estimate pharmacokinetic and pharmacodynamic parameters of central nervous system drugs is reviewed in this article. BMC is a mode of micellar liquid chromatography, MLC, that uses micellar mobile phases of Brij35 (polyoxyethilene(23) lauryl ether) prepared in physiological conditions (pH, ionic strength). The retention of a drug in this system depends on its hydrophobic, electronic and steric properties, which also determine its biological activity. The results of BMC studies suggest that this in vitro approach is an attractive useful tool to be implemented into the lead optimization step of drug development sc…
A density functional study of flavonoid compounds with anti-HIV activity.
2005
Abstract Quantum chemical calculations at the DFT/B3LYP theory level, with the 6-31G* basis set, was employed to calculate a set of molecular properties of 26 flavonoid compounds with anti-HIV activity. The correlation between biological activity and structural properties was obtained by using the multiple linear regression method. The model obtained showed not only statistical significance but also predictive ability. We demonstrate in this paper that the anti-HIV activity of compounds can be related with the molecular hydrophobicity (ClogP), the electronegativity ( χ ) and the charges on some key atoms, while that the toxicity can be related with the electronic affinities (EA), ClogP and …
Prediction of tyrosinase inhibition activity using atom-based bilinear indices.
2007
A set of novel atom-based molecular fingerprints is proposed based on a bilinear map similar to that defined in linear algebra. These molecular descriptors (MDs) are proposed as a new means of molecular parametrization easily calculated from 2D molecular information. The nonstochastic and stochastic molecular indices match molecular structure provided by molecular topology by using the kth nonstochastic and stochastic graph-theoretical electronic-density matrices, M(k) and S(k), respectively. Thus, the kth nonstochastic and stochastic bilinear indices are calculated using M(k) and S(k) as matrix operators of bilinear transformations. Chemical information is coded by using different pair com…
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method
2003
Objectives: In order to select new drugs and to predict their in vitro activity against Mycobacterium avium complex (MAC), new quantitative structure-activity relationship (QSAR) models were developed. Methods: The activities against MAC of 29 structurally heterogeneous drugs were examined by means of linear discriminant analysis (LDA) and multilinear regression analysis (MLRA) by using topological indices (TI) as structural descriptors. In vitro antimycobacterial activities were determined by a broth microdilution method with 7H9 medium. Results: The topological model obtained successfully classifies over 80% of compounds as active or inactive; consequently, it was applied in the search fo…
3D-QSAR pharmacophore modeling and in silico screening of new Bcl-xl inhibitors.
2010
Bcl-2 proteins family members play several roles in tumoral proliferation: they inhibit proapoptotic activity during oncogenesis, support tumor cells survival, induce chemoresistance. The discovery of new small inhibitors of Bcl-xl represents a new frontier for cancer treatment. In this study, a 3D-QSAR pharmacophore model was developed, based on 42 biarylacylsulfonamides, and used to understand the structural factors affecting the inhibitory potency of these derivatives. Aromatic, negative charge, and hydrogen bond acceptor effects contribute to the inhibitory activity. The model was then employed as 3D search query to screen ZINC drug-like database in order to select new scaffolds. Finall…
A topological sub-structural approach for predicting human intestinal absorption of drugs.
2004
The human intestinal absorption (HIA) of drugs was studied using a topological sub-structural approach (TOPS-MODE). The drugs were divided into three classes according to reported cutoff values for HIA. "Poor" absorption was defined as HIAor =30%, "high" absorption as HIAor =80%, whereas "moderate" absorption was defined between these two values (30%HIA79%). Two linear discriminant analyses were carried out on a training set of 82 compounds. The percentages of correct classification, for both models, were 89.02%. The predictive power of the models were validated by three test: a leave-one-out cross validation procedure (88.9% and 87.9%), an external prediction set of 127 drugs (92.9% and 80…
Prediction of Aquatic Toxicity of Benzene Derivatives to Tetrahymena pyriformis According to OECD Principles
2016
Background: Many QSAR studies have been developed to predict acute toxicity over several biomarkers like Pimephales promelas, Daphnia magna and Tetrahymena pyriformis. Regardless of the progress made in this field there are still some gaps to be resolved such as the prediction of aquatic toxicity over the protozoan T. pyriformis still lack a QSAR study focused in accomplish the OECD principles. Methods: Atom-based quadratic indices are used to obtain quantitative structure-activity relationship (QSAR) models for the prediction of aquatic toxicity. Our models agree with the principles required by the OECD for QSAR models to regulatory purposes. The database employed consists of 392 substitut…
New Hypolipaemic Agents Designed by Molecular Topology: Pharmacological Studies of 2,6-Di-tert-butyl-4-methylpyridine and 2,6-Di-tert-butylpyridine
1999
New compounds showing hypolipaemic activity have been designed using a computer-aided method based on molecular topology and QSAR analysis. Linear discriminant analysis and connectivity functions were used to design three potentially suitable drugs which were tested for hypolipaemic properties by the Triton WR-1339 test in rats. The pharmacological tests carried out on the newly designed compounds demonstrated the existence of notable activity in phase I for two of them. namely 2,6-Di-tert-butyl-4-methylpyridine (C.A.S. 38222-83-2) and 2,6-Di-tert-butylpyridine (C.A.S. 585-48-8), with respect to the level of total cholesterol. Both substances decrease the lipaemia to lower levels than clofi…
Introduction to molecular topology: basic concepts and application to drug design.
2012
In this review it is dealt the use of molecular topology (MT) in the selection and design of new drugs. After an introduction of the actual methods used for drug design, the basic concepts of MT are defined, including examples of calculation of topological indices, which are numerical descriptors of molecular structures. The goal is making this calculation familiar to the potential students and allowing a straightforward comprehension of the topic. Finally, the achievements obtained in this field are detailed, so that the reader can figure out the great interest of this approach.