MOLECULAR MODELING STUDIES OF THIAZOLE DERIVATIVES AS PIN1 INHIBITORS

Peptidyl-prolyl cis-trans isomerase NIMA - interacting 1 (PIN1) appeared as a potential therapeutic target in Alzheimer disease, cardiovascular disease and various types of cancer (breast, colon, prostate, esophagus, cervical, etc.). We performed 3D shape similarity search and pharmacophore modeling studies for a series of thiazole derivatives PIN1 inhibitors. A five-point pharmacophore (ADRRR.2) displaying one hydrogen bond acceptor (A), one hydrogen bond donor (D), and three aromatic rings (R) was obtained. Atom-based 3D-QSAR model associated to this hypothesis show significant statistical parameters (training set: R-squared = 0.839, the standard error of estimates, SD = 0.132; test set: correlation coefficient Q-squared = 0.569 and Pearson-R = 0.825. 3D Shape similarity alignment provide information about the possible orientation of these compounds into PIN1 binding site. The pharmacophore hypothesis ADRRR.2, atom-based 3D QSAR and shape similarity search is expected to guide the rational design of novel thiazole derivatives with enhanced affinity towards PIN1.