Cross Docking Study Directed Towards Virtual Screening and Molecular Docking Study of Phenanthrene 1,2,4-triazine Derivatives As Novel Bcl-2 Inhibitors

Apoptosis is critical for tissue homeostasis and also for the physiological removal of abnormal cells. Bcl-2 family proteins are important regulators of apoptosis. It is observed that antiapototic Bcl-2 family members are generally overexpressed in many cancer cells. As a result, it has motivated a growing interest in the discovery of small molecules targeting such proteins as potential anticancer therapeutics. With the aim of designing new phenanthrene based Bcl-2 inhibitors, we performed a cross-docking study. This study followed by virtual screening is conducted for different available Bcl-2 X-ray crystal structures in order to find the most appropriate PDB code of this enzyme. After analytical analysis, the selected crystal structure was used to screen the library of phenanthrene triazine based structures containing different substitutions attached to the hydrazone moiety. The ligand which interacts with the target with the lowest binding energy was determined. The lowest binding energy was -10.19 kcal/mol. As a conclusion, cross docking study could be a validated strategy for finding the most appropriate crystal structure for docking study and the virtual screening of the designed library indicates the best ligand for the specified target. Our designed library of phenanthrene triazine-based derivatives containing hydrazone pendant, could be served as potential candidates for Bcl-2 inhibition.