Identification of novel anti-cancer agents, applying in silico method for SENP1 protease inhibition

The SENP1 (Sentrin-Specific Protease1) is essential for desumoylation. SENP1 plays an essential role in many diseases such as cardiovascular disease, diabetes and cancer via targeting GATA2, NEMO, Pin1, SMAD4 and HIF-1α for deSUMOylation. Considering that, over expression of SENP1 was reported in cancer, thus an optional inhibitor of SENP1 can restitute the balance to the skewed system of SUMO and act as an effective therapeutic agent. The purpose of this study was to select and to sort inhibitors with a stronger binding affinity with SENP1. Molecular docking of SENP1 with natural compounds including Gallic acid, Caffeic acid, Thymoquinone, Thymol, Betaine, Alkannin, Ellagic acid, Betanin, Shikonin, Betanidin and Momordin IC was performed using AutoDock 4, then docking complexes for molecular dynamics (MD) simulation with GROMACS 4.6.5 were applied. Results with RMSD, RMSF, SASA, DSSP, gyrate, H-bond, ADMET and TOPKAT measurements, binding energy and structural features were surveyed. Among those, Gallic acid has shown the most significant results including RMSD and RMSF plots with high stability, high hydrogen bonds, high binding energy and the highest intermolecular bonds with SENP1. Gallic acid demonstrated strong connections and results of toxicity better than Momordin as control. Gallic acid is a phenolic compound which affects several pharmacological and biochemical pathways and has strong antioxidant, anti-inflammatory, antimutagenic and anticancer properties. Further research can improve the appropriate use of plant products drastically. Basic, pre-clinical and clinical research on Gallic acid may provide a roadmap for its ultimate application in the field of cancer prevention. Communicated by Ramaswamy H. Sarma