Quantitative structure-activity relationship models with receptor-dependent descriptors for predicting peroxisome proliferator-activated receptor activities of thiazolidinedione and oxazolidinedione derivatives

• Autor(a) principal: Lather, Viney
• Data de Publicação: 2009
• Outros Autores: Kairys, Visvaldas, Fernandes, Miguel X.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.13/5011
• topic: Multiple linear regression; Peroxisome proliferator-activated receptor,; Quantitative structure–activity relation; .; Faculdade de Ciências Exatas e da Engenharia

A quantitative structure–activity relationship study has been carried out, in which the relationship between the peroxisome proliferator-activated receptor a and the peroxisome proliferator activated receptor c agonistic activities of thiazo lidinedione and oxazolidinedione derivatives and quantitative descriptors, Vsite calculated in a receptor-dependent manner is modeled. These descriptors quantify the volume occupied by the optimized ligands in regions that are either com mon or specific to the superimposed binding sites of the targets under consideration. The quantita tive structure–activity relationship models were built by forward stepwise linear regression model ing for a training set of 27 compounds and vali dated for a test set of seven compounds, resulting in a squared correlation coefficient value of 0.90 for peroxisome proliferator-activated receptor a and of 0.89 for peroxisome proliferator-activated receptor c. The leave-one-out cross-validation and test set predictability squared correlation coeffi cient values for these models were 0.85 and 0.62 for peroxisome proliferator-activated receptor a and 0.89 and 0.50 for peroxisome proliferator-acti vated receptor c respectively. A dual peroxisome proliferator-activated receptor model has also been developed, and it indicates the structural features required for the design of ligands with dual peroxisome proliferator-activated receptor activity. These quantitative structure–activity relationship models show the importance of the descriptors here introduced in the prediction and interpretation of the compounds affinity and selectivity.