Refinement and Use of the Approximate Similarity in QSAR Models for Benzodiazepine Receptor Ligands

Abstract

Several considerations for refining the approximate similarity measurements have been introduced in this paper: the use of topological invariants for the calculation of similarity indexes and the development of new similarity correction processes. The quality of the new similarity measurements obtained with the proposed methods has permitted the development of fast, cheap, and simple quantitative structure-activity relationship models for the prediction of biological activities of nonbenzodiazepine gamma-aminobutyric acid(A)/benzodiazepine receptor ligands (58 compounds). Internal and external validations were carried out for the approximate similarity matrices computed using different approaches. Satisfactory results which compare reasonably well with a 3D approach were obtained: Q2= 0.65 and standard error in cross validation SECV= 0.83 for the training stage; r = 0.79 and error in external prediction = 0.82 for the test step. In addition, the method proposed was compared with other topological approaches based on constitutional similarity and on fingerprints. Satisfactory results were obtained.

Data Fusion of Similarity and Dissimilarity Measurements Using Wiener-Based Indices for the Prediction of the NPY Y5 Receptor Antagonist Capacity of Benzoxazinones

“…They employed those descriptors showing high correlations with the activity under study and different similarity measures weighted by optimal consensus factors. In previous works, ,, we have shown the usefulness of the approximate similarity (AS) concept to develop QSAR models. Approximate similarity is based on correcting constitutional similarities by means of distance or dissimilarity values corresponding to the nonisomorphic fragments extracted from matching processes.…”

“…One of the most employed similarity measurements is based on mapping fragments of a molecule into bits of a binary string (fingerprint). − It has been shown that fingerprints provide a nonintuitive encoding of molecular size, shape, and global similarity. Other common similarity measurements are based on the isomorphism calculation (e.g., maximum common substructure), and recently, similarity measurements which employ distances between topological descriptors computed over 2D molecular representations have also been proposed. − Through the use of these representations above, different similarity indices have been studied (e.g., Tanimoto, cosine, Raymond, etc.) to generate similarity values…”

Advantages of Relative versus Absolute Data for the Development of Quantitative Structure–Activity Relationship Classification Models

“…This kind of proposal has also been used in other papers that use relative measurements and allow the generation of data representations that include a refinement that favors the development of other QSAR models.…”

Indolo[3,2-a]carbazoles from a Deep-Water Sponge of the Genus Asteropus

“…No biological activity was reported for ancorinazole, but a series of synthetic indolo[3,2- a ]carbazoles have been predicted to block binding of benzodiazepine to the γ-aminobutyric acid A/benzodiazepine receptor. 13,14 Screening of these naturally occurring metabolites in such an assay system could identify new lead structures for the development of medicines to target neurological and psychiatric disorders.…”