Prediction of new Hsp70 inhibitors based on quinazoline scaffold by virtual screening method

Background and objective : Heat shock proteins (Hsps) are an extremely evolutionarily preserved group of chaperone proteins. Hsps are categorized into families by their molecular weights: Hsp100, 90, 70, 60, 40, and small Hsps. Hsp70 plays many roles in cellular processes, including the correct folding of denatured proteins to avoid their aggregation and ubiquitination (1). Following the cellular stresses, the expression levels of Hsp70 are increased, thus inhibition of Hsp70 would be a good treatment for cancer disease (2). Many compounds (natural and synthetic) have introduced as Hsp70 inhibitors, among these, we chose quinazoline as lead compound for virtual screening studies (3). Search Methods : 1000 compounds with quinazoline scaffold were chosen from ZINC (www.zinc.docking.org) database that were filtered using Lipinski’s rules. The first, docking validation was performed by re-docking co-crystallized ligand with Hsp70 protein (PDB ID: 4IO8) by AutoDock 4.2. Then, virtual screening was done. Findings: All of the results were sorted in terms of the binding energy and orientation of ligands in the active site of the Hsp70 protein. The best ligands according to the binding energy and the essential interactions with the active site were chosen. Conclusion :The findings indicate that new quinazoline compounds were perched in Hsp70 active site and we can introduce them as new Hsp70 inhibitors for future studies.

کلیدواژه ها:

Hsp70 inhibitor ، Docking ، Virtual screening