Exploring the binding affinity and non-covalent interactions of anthocyanins with aging-related enzymes through molecular docking

Abstract

Background and Objective: Anthocyanins are associated with aging and longevity. However, the mechanism involving the pure anthocyanin compounds in aging remains elusive. To investigate the possible mechanism of action of the different anthocyanin compounds towards aging-associated enzymes, the lead-likeness, binding affinity, and binding interactions were evaluated.

Methodology: The different anthocyanin compounds such as cyanidin, delphinidin, malvidin, pelargonidin,
peonidin, and petunidin were assessed for lead-likeness following the criteria of Lipinski's rule of five (Ro5).
These same compounds were virtually docked to different aging-related enzymes involved in MAPK, AMPK,
and insulin signaling pathways. The top binding anthocyanins for each enzyme were visualized and compared to the enzyme inhibitors.

Results: The different anthocyanin compounds abide with Ro5 denoting its potential as a lead compound. For each enzyme, there were different top-binding anthocyanins. The crystal structures of the docked
anthocyanins reveal that there were different substructures involved during the non-covalent interaction.
Some substructures, particularly the hydroxy groups, have different roles during the H-bond formation. These findings suggest that the various anthocyanin compounds may have a distinct mechanism of action towards a specific enzyme.

Conclusion: Taken together, these results suggest that the anthocyanin compounds may have varying effects in aging enzymes, which may be due to the differences in their substructures. Nonetheless, further investigations are needed to understand these findings using cells and animal models.