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Bond‐based 3D‐chiral linear indices: Theory and QSAR applications to central chirality codification
Author(s) -
CastilloGarit Juan A.,
MarreroPonce Yovani,
Torrens Francisco,
GarcíaDomenech Ramón,
RomeroZaldivar Vicente
Publication year - 2008
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20964
Subject(s) - quantitative structure–activity relationship , chirality (physics) , computational chemistry , bond , chemistry , stereochemistry , physics , quantum mechanics , economics , chiral symmetry , finance , nambu–jona lasinio model , quark
The recently introduced non‐stochastic and stochastic bond‐based linear indices are been generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D‐chirality correction factor. These improved modified descriptors are applied to several well‐known data sets to validate each one of them. Particularly, Cramer's steroid data set has become a benchmark for the assessment of novel quantitative structure activity relationship methods. This data set has been used by several researchers using 3D‐QSAR approaches such as Comparative Molecular Field Analysis, Molecular Quantum Similarity Measures, Comparative Molecular Moment Analysis, E‐state, Mapping Property Distributions of Molecular Surfaces, and so on. For that reason, it is selected by us for the sake of comparability. In addition, to evaluate the effectiveness of this novel approach in drug design we model the angiotensin‐converting enzyme inhibitory activity of perindoprilate's σ‐stereoisomers combinatorial library, as well as codify information related to a pharmacological property highly dependent on the molecular symmetry of a set of seven pairs of chiral N ‐alkylated 3‐(3‐hydroxyphenyl)‐piperidines that bind σ‐receptors. The validation of this method is achieved by comparison with earlier publications applied to the same data sets. The non‐stochastic and stochastic bond‐based 3D‐chiral linear indices appear to provide a very interesting alternative to other more common 3D‐QSAR descriptors. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008