Search results for "Polar surface area"
showing 5 items of 5 documents
In silico prediction of central nervous system activity of compounds. Identification of potential pharmacophores by the TOPS–MODE approach
2004
The central nervous system (CNS) activity has been investigated by using a topological substructural molecular approach (TOPS-MODE). A discriminant analysis to classify CNS and non-CNS drugs was developed on a data set (302 compounds) of great structural variability where more than 81% (247/302) were well classified. Randic's orthogonalization procedures was carried out to allow the interpretation of the model and to avoid the collinearity among descriptors. The discriminant model was assessed by a leave-n-out (when n varies from 2 to 20) cross-validation procedure (79.94% of correct classification), an external prediction set composed by 78 CNS/non-CNS drugs (80.77% of correct classificati…
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…
The Use of Rule-Based and QSPR Approaches in ADME Profiling: A Case Study on Caco-2 Permeability.
2013
During the early ADME profiling the development of simple, interpretable and reliable in silico tools is very important. In this study, rule-based and QSPR approaches were investigated using a large Caco-2 permeability database. Three permeability classes were determined: high (H), moderate (M) and low (L). The main physicochemical properties related with permeability were ranked as follows: Polar Surface Area (PSA)>Lipophilicity (logP/logD)>Molecular Weight (MW)>number of Hydrogen Bond donors and acceptors>Ionization State>number of Rotatable Bonds>number of Rings. The best rule, based on the combination of PSA-MW-logD (3PRule), was able to identify the H, M and L classes with accuracy of …
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…
A Slightly Modified Expression of the Polar Surface Area Applied to an Olfactory Study
2013
The polar surface area of a molecule is currently defined as the surface sum over all polar atoms, primarily oxygen and nitrogen, also including their attached hydrogens (named PSA1 in the present study). Some authors also include sulfur and phosphor (PSA3). The slight modification suggested here is based on the fact that it is difficult to consider, on a theoretical point of view, hexavalent S and pentavalents N and P as polar atoms. Indeed, in these cases, all their peripheral electrons are involved in bondings. We propose to define PSA2 using the initial definition extended to O, S, N, P, with the exception of hexavalent S and pentavalents N and P. In order to test this hypothesis, the t…