title: Molecular docking and CoMFA studies of thiazoloquin(az)olin(on)es as CD38 inhibitors: determination of inhibitory mechanism, pharmacophore interactions, and design of new inhibitors.
abstract: In this research, molecular docking and 3D-QSAR studies were carried out on a series of 79 thiazoloquin(az)olin(on)es as CD38 inhibitors. Based on docking results, four interactions including hydrogen bonding with main chain of GLU-226 (H-M-GLU-226), Van der Waals interactions with side chain of TRP-125 (V-S-TRP-125), TRP-189 (V-S-TRP-189), and THR-221 (V-S-THR-221) were considered as pharmacological interactions. Active conformation of each ligand was extracted from docking studies and was used for carrying out 3D-QSAR modeling. Comparative molecular field analysis (CoMFA) was performed on CD38 inhibitory activities of these compounds on human and mouse. We developed CoMFA models with five components as optimum models for both data-sets. For human data-set, a model with high predictive power was developed. R2, RMSE, and F-test values for training set of this model were .94, .24, and 179.58, respectively, and R2and RMSE for its test set were .92 and .32, respectively. The q2and RMSE values for leave-one-out cross validation test on training set were .78 and .46, respectively, that demonstrate created model is robust. Based on extracted steric and electrostatic contour maps for this model, three inhibitors with pIC50larger than 8.85 were designed.
authors: a Faculty of Science, Department of Chemistry , University of Kurdistan , P.O. Box 416 , Sanandaj , Iran.
authors: Bakhtyar
authors: B
authors: Sepehri
authors: a Faculty of Science, Department of Chemistry , University of Kurdistan , P.O. Box 416 , Sanandaj , Iran.
authors: Raouf
authors: R
authors: Ghavami
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D008024:Ligands; D062105:Molecular Docking Simulation; D011487:Protein Conformation / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D008024:Ligands; D013844:Thiazoles; D051997:ADP-ribosyl Cyclase 1
keywords: CD38; CoMFA; molecular docking; pharmacophore; thiazoloquin(az)olin(on)es