Docking-based 3D-QSAR (CoMFA, CoMFA-RG, CoMSIA) study on hydroquinoline and thiazinan-4-one derivatives as selective COX-2 inhibitors

Abstract

A series of 26 selective COX-2 inhibitors which reported previously by our laboratory was selected to generate three-dimensional quantitative structure activity relationship (3D-QSAR) model. Active conformation of each molecule was predicted by docking studies and used for molecular alignment. Activity of 20 molecules as a train set was predicted using three methods including comparative molecular field analysis (CoMFA), CoMFA region focusing (CoMFA-RG) and comparative molecular similarity index analysis (CoMSIA). The best models of CoMFA-RG and CoMSIA revealed correlation coefficients r of 0.955 and 0.947, the leave one out cross-validation coefficients q of 0.573 and 0.574, respectively. In addition, CoMFA-RG and CoMSIA models were validated by a test set of six molecules with predicted coefficients r of 0.644 and 0.799, respectively. Contour maps of generated models provided fruitful information about structural aspect of molecules that affected their COX-2 inhibitory activity. Based on three models results, steric and electrostatic properties are the most important factors in controlling the activity of the molecules. Results of CoMFA-RG and CoMSIA models were utilized to design new molecules. Comparison of experimental and predicted pIC values of designed molecules indicated that CoMFA-RG had the more predictive ability. Communicated by Ramaswamy H. Sarma.

Phytochemical Characterization, Antioxidant and Anti-Inflammatory Effects of Cleome arabica L. Fruits Extract against Formalin Induced Chronic Inflammation in Female Wistar Rat: Biochemical, Histological, and In Silico Studies

“…This may justify their important role in the COX-2 binding and inhibition during the inflammatory process [68]. The 3D illustration and the 2D diagram of interactions exhibit that the selected compounds are bound to COX-2 through a network of electrostatic, hydrophobic and hydrogen bonds [69]. In addition, all the compounds evaluated showed negative binding energy, which may explain the Cleome anti-inflammatory effect as described by the biochemical and histological tests.…”

Comparative Molecular Field Analysis (CoMFA), Molecular Docking and ADMET Study on Thiazolidine-4-carboxylic acid Derivatives as New Neuraminidase Inhibitors

“…The variability of bioactivity rates and biological properties was also taken into account when randomly partitioning the training and test sets. 17 (Table 1).…”

Research on the Anti-tumor Activity of Novel Histone Deacetylase Inhibitors based on 3D QSAR Model

“…In the present QSAR research, a total of 71 HDAC inhibitors and related bioactivities were gathered from the work reported in the literature [19]. The experimental IC 50 values were converted into pIC 50 (-log IC 50 ) values as dependent variable and QSAR descriptors of CoMFA and CoMSIA were expressed as independent variables in 3D-QSAR analysis [20]. The chemical structures and corresponding biological data of all compounds are presented in Table 1.…”