Background: Cancer is a well-known and well-studied disease. There are environmental
as well as genetic factors that trigger cancer. All forms of cancer are associated with the deregulation
of genes and proteins. Aldose reductase, Aldose Reductase like protein 1 and Aldehyde Reductase
are homologous proteins that are overexpressed in different types of cancer. They are NADPHdependent
oxidoreductases. The active site is conserved, thus there is very less substrate specificity
among those proteins. In this study, novel molecules targeting the three proteins are designed.
Method: LigBuilder V2 software is used to design novel molecules. Molecular docking is performed
to study the binding affinity of each ligand towards the targets. Molecular Dynamics Simulation was
done to check the stability of protein-ligand complexes in an aqueous environment.
Result: Six novel molecules have been designed. The six molecules studied are found to have better
in silico affinity than tolrestat (known inhibitor). The designed molecules are predicted to be orally
active. Finally, Molecular Dynamics Simulation showed that the protein-ligand complexes are stable
in an aqueous environment.
Conclusion: New molecules targeting Aldose reductase, Aldose Reductase like protein 1 and Aldehyde
Reductase have been designed.