QSAR correlation

OASIS (optimized approach based on structural indices set) has been developed by Mekenyan and co-workers [87]. Given the activities or toxicities of a set of compounds, it generates large numbers of structural indices for each and develops QSAR correlations. The approach has been used to model the acute toxicity of industrial chemicals [88]. It is claimed [89] that the method can be of use in elucidating mechanisms of action. 

Theoretical calculations can also provide physicochemical data, which can be used as an input for 3D-QSAR correlation studies [134,141]. There is a current trend in the area of lead-finding in the pharmaceutical industry to use calculations to set up computer search profiles to be used in the screening of large structural databases, such as the chemical suppliers databases and the internal company databases. 

We discussed the extrathermodynamic relationships that provide a common basis for most of the parameters used in QSAR. We have presented a critical analysis of the empirical framework for the derivation of these parameters and a rationale for choosing them. The analysis of the physicochemical basis of the parameters and of the methods shows the caution needed in interpreting molecular mechanisms from QSAR correlations. 

Structure-activity relationship (SAR) studies are based on the assumption that similar molecules elicit similar activities in a lock/key-type manner. Quantitative structure-activity relationships (QSARs) correlate the extent of a change in a biological response (e.g., activity) elicited by a specific compound with its physicochemical and/or its structural properties,... 

It can be noted that function i was used by Ivanciuc to define the —> distance-valency matrices, function was used by Kier-Hall to define the —> electrotopological state indices, function y was proposed by Randic to calculate the —> alimented valence of vertices, and function y was proposed by Estrada in the generalized molecular-graph matrix, where x is a user-defined parameter or a parameter to be optimized during the searching for the best QSAR correlations. 

QSAR used bulk properties of the potential drug molecules. A more recent method, 3D-QSAR, correlates activity with properties that depend on particular parts of the molecular structure such as the electrostatic potential. In 3D-QSAR a set of molecules of known activity is superimposed by computer so that similar groups in each molecule are in the same place. A box is drawn that contains all the molecules... 

The earliest successful biological QSAR correlating plant growth regulating activity of X-phenoxyacetic acids utilized Hammett sigma constants for electronic effects and pi-constants for hydrophobicity. Pi (designated by lower case Tt) for the most common substituents was taken as the difference in the... 

QSAR Correlation. Statistical quality of QSAR correlation can be employed as a third criterion of commonality of mechanism. This approach can prove very meaningful when coupled with a mechanistic interpretation of the role of molecular descriptors used in the correlation, and with the significance of the slope and intercept. The quality of statistical fit and the interpretation of the parameter or parameters used in the correlation can provide a valuable insight into molecular mechanism. Recently, Hansch analysis has been combined with molecular graphics and modeling studies in which the activities of a series of substrates to an enzyme receptor have been related to the hydrophobic, electronic, and steric requirements for reversible binding... 

Narcosis represents the most fundamental molecular mechanism of the toxicity of nonelectrolyte organic compounds. QSAR correlations derived... 

M. Randic, J. Markelj, and M. Pompe, Traditional and non traditional QSAR correlations revisited, SAR QSAR Environ. Chem. (to be submitted). 

Classical QSAR correlates biological activities of drugs with physicochemical properties or indicator variables which... 

Quantitative structure-activity relationships (QSAR) correlate the dependence of various biological activities on different physicochemical properties (Hansch analysis, extrathermo-dynamic approach) or on the presence and absence of certain structural features (Free-Wilson analysis). " In addition, the concept of Hansch analysis is used to correlate different biological activities, e.g., in vitro and in vivo, with each other. ... 

Yan C, Han M, Wan H, Guan G (2010) QSAR correlation of the melting points for imidazolium bromides and imidazolium chlorides ionic liquids. Fluid Phase Equilib 292 104-109... 

By selecting the highest QSAR correlation among SMILES screening based compounds ... 

This way, the common representation of the structural formulas through the graph characteristics is constructing specific matrices for them, some of them with clear physical interpretation while other being less intuitive, however, still most helpful in QSAR correlations (Putz et al., 2008b). 

FIGURE 3.28 Illustration of the molecular mechanism for genotoxic carcinogenesis according to the present residual-QSAR correlation-path hierarchy superimposed over an immunohistochemcial analysis of paraffin-embedded sections of rat intestinal cancer (Putz, 2011a) using the Caspase-2 antibody (2011). 

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