Application of 3D QSAR and Docking Studies in Optimization of Perylene di imides as Anti Cancer Agent

Abstract:

Introduction: Telomerase is an enzyme which binds to telomeres and increases its length which leads to extension of lifespan of cells. These enzymes are expressed at detectable levels in cancer cells which makes an attractive target for cancer therapy. The G Quadruplex ligands which bind to telomerase with respect to duplex genomic DNA is of special importance. The Perylene di imides are selected, designed and QSAR study has been done, finally from the QSAR results’ docking has been done by G4LDB database. To compare and to narrow down the Docking results from G4LDB database, we have chosen AutoDock tool by selecting a target Telomerase protein (PDB ID: 4B18) to analyse the binding affinity of the protein with respect to the Perylene diimides. The best scored compounds will be efficient for designing new molecules as well as for the anti-cancer therapy. Material: G4LDB Database, AutoDock 4.2, Discovery Studio Visualizer 4.1. Methods: The study was to investigate and compare the results from G4LDB database with the AutoDock results for anti cancer activity of Perylene di imides. The results are visualized by Discovery Studio 4.1 Visualizer. Compound 20 and compound 48 shows best ligand interaction with the selected targets from G4LDB database. From the AutoDock results the compounds are docked with the specific Telomerase protein 4B18 and Compound 11 shows good binding energy when compared with the PIPER. Results: Compounds 11, 20 and 48 showed good biological activity also possessing best binding affinity with the target. Discussion: From the QSAR and Docking studies (G4LDB and AutoDock), 3 compounds (11, 20 and 48) showed good biological activity possessing a strong correlation coefficient, endorses that Perylene derivatives are having strong affinity with the targets. Docking has been done from the results of QSAR study, targeting Telomerase protein to study the binding affinity with the target. Conclusion: From the results, the best compounds will be efficient to inhibit telomerase enzyme and these compounds can be used to design new molecules which will be effective for anticancer therapy.

Key words: Perylene Derivatives, QSAR Plus, G-Quadruplex Ligand Database, Docking.