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

Title:In silico Designing of Novel Inhibitors for Triple Inhibition of Aldose Reductase, Aldose Reductase Like Protein 1, and Aldehyde Reductase

Volume: 16 Issue: 6

Author(s): Arpita Devi*

Affiliation:

• Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur PIN-784028, Assam,India

Keywords: Cancer, aldose reductase, aldose reductase like protein 1, aldehyde reductase, docking, molecular dynamics simulation.

Abstract:

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.

Methods: 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.

Results: 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.

Cite this article as:

Devi Arpita*, In silico Designing of Novel Inhibitors for Triple Inhibition of Aldose Reductase, Aldose Reductase Like Protein 1, and Aldehyde Reductase, Current Computer-Aided Drug Design 2020; 16 (6) . https://dx.doi.org/10.2174/1573409915666191015111200