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Quantitative structure-activity relationship models with receptor-dependent descriptors for predicting peroxisome proliferator-activated receptor activities of thiazolidinedione and oxazolidinedione derivatives
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Advisor(s)
Abstract(s)
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.
Description
Keywords
Multiple linear regression Peroxisome proliferator-activated receptor, Quantitative structure–activity relation . Faculdade de Ciências Exatas e da Engenharia
Citation
Lather, V., Kairys, V., & Fernandes, M. X. (2009). Quantitative structure-activity relationship models with receptor-dependent descriptors for predicting peroxisome proliferator-activated receptor activities of thiazolidinedione and oxazolidinedione derivatives. Chemical biology & drug design, 73(4), 428-441.
Publisher
Wiley