Exploring QSAR for Substituted 2‐Sulfonyl‐Phenyl‐Indol Derivatives as Potent and Selective COX‐2 Inhibitors Using Different Chemometrics Tools

Abstract

Selective inhibition of cyclooxygenase-2 inhibitors is an important strategy in designing of potent anti-inflammatory compounds with significantly reduced side effects. The present quantitative structure-activity relationship study, attempts to explore the structural and physicochemical requirements of 2-sulfonyl-phenyl-indol derivatives (n = 30) for COX-2 inhibitory activity using chemical, topological, geometrical, and quantum descriptors. Some statistical techniques like stepwise regression, multiple linear regression with factor analysis as the data preprocessing (FA-MLR), principal component regression analysis, and genetic algorithms partial least squares analysis were applied to derive the quantitative structure-activity relationship models. The generated equations were statistically validated using cross-validation and external test set. The quality of equations obtained from stepwise multiple linear regression, FA-MLR, principal component regression analysis and PLS were in the acceptable statistical range. The best multiple linear regression equation obtained from factor analysis (FA-MLR) as the preprocessing step could predict 77.5% of the variance of the cyclooxygenase-2 inhibitory activity whereas that derived from genetic algorithms partial least squares could predict 84.2% of variances. The results of quantitative structure-activity relationship models suggested the importance of lipophilicity, electronegativity, molecular area and steric parameters on the cyclooxygenase-2 inhibitory activity.

QSAR analysis of diaryl COX-2 inhibitors: Comparison of feature selection and train-test data selection methods

“…However, the use of specific COX-2 selective drugs was a failure owing to their cardiovascular side effects that occurred because of the inhibition of prostaglandins secretion which is required for the normal functioning of the cardiovascular system and is produced by COX-1 isoform [3].…”

A QSAR Study for Analgesic and Anti‐inflammatory Activities of 5‐/6‐Acyl‐3‐alkyl‐2‐Benzoxazolinone Derivatives

“…Khoshneviszadeh et al. modeled COX‐2 inhibitory activity using Petitjean index along with other molecular descriptors …”

Chemometrics tools in QSAR/QSPR studies: A historical perspective

“…As a solution to this limitation for example in PCA, using of the loadings of the selected principal components has been suggested to obtain the variables of high loading values [325,326]. Also, instead of application of feature extraction methods on whole data set, Hemmateenejad et al suggested partitioning of variables into different subsets firstly and then running of PCA on each subset, separately.…”