In silico Designing of Novel Inhibitors for Triple Inhibition of Aldose Reductase, Aldose Reductase Like Protein 1, and Aldehyde Reductase | Bentham Science

摘要

Background: Cancer is a well-known and well-studied disease. There are environmentalas well as genetic factors that trigger cancer. All forms of cancer are associated with the deregulationof genes and proteins. Aldose reductase, Aldose Reductase like protein 1 and Aldehyde Reductaseare homologous proteins that are overexpressed in different types of cancer. They are NADPHdependentoxidoreductases. The active site is conserved, thus there is very less substrate specificityamong those proteins. In this study, novel molecules targeting the three proteins are designed.Methods: LigBuilder V2 software is used to design novel molecules. Molecular docking is performedto study the binding affinity of each ligand towards the targets. Molecular Dynamics Simulationwas done to check the stability of protein-ligand complexes in an aqueous environment.Results: Six novel molecules have been designed. The six molecules studied are found to have betterin silico affinity than tolrestat (known inhibitor). The designed molecules are predicted to be orallyactive. Finally, Molecular Dynamics Simulation showed that the protein-ligand complexes are stablein an aqueous environment.Conclusion: New molecules targeting Aldose reductase, Aldose Reductase like protein 1 and AldehydeReductase have been designed.