Exploration of Novel Human Tyrosinase Inhibitors by Molecular Modeling, Docking and Simulation Studies

Research studies on human tyrosinase inhibitors and exploration for better cytotoxic agents remain an important line in drug discovery and development at the present time. Recently, multiple inhibitors are being used to cure melanogenesis by targeting human tyrosinase. A series of coumarin (C1–C9)-, thymol (T1–T8)- and vanillin (V1–V8)-based derivatives have been theoretically analyzed for their inhibitory effects against human tyrosinase. The crystal structure of human tyrosinase is not available in Protein Data Bank. Therefore, homology modeling approach was used to predict three-dimensional (3D) crystal structure of human tyrosinase. The reliability and efficacy of predicted 3D structure were validated by using Ramachandran plots which indicate that 95.01 % residues are present in favored regions. Moreover, multiple computational approaches such as molecular docking and molecular dynamic (MD) simulation along with various online tools were employed to screen the best inhibitor against melanogenesis. The results revealed that V7 and C9 compounds showed significant binding energy values (−7.79 and −7.40 kcal/mol, respectively) compared with the standard drugs such as kojic acid (−4.21 kcal/mol) and arbutin (−4.62 kcal/mol). Moreover, MD simulation results also justified that V7 showed little fluctuations throughout the simulation period as depicted by the root mean square deviation and root mean square fluctuation graphs. Thus, the present in silico study provides a deeper insight into the structural attributes of V7 compound and its overall molecular interactions against human tyrosinase and gives a hypothetical gateway to use this compound as a potential inhibitor against melanogenesis.