Background: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is an enzyme
that isomerizes phosphorylated serine or threonine motifs adjacent to proline residues. Pin1
has important roles in several cellular signaling pathways, consequently impacting the development
of multiple types of cancers.
Methods: Based on the previously reported inhibitory activity of pentacyclic triterpenoids isolated
from the gum resin of Boswellia genus against Pin1, we designed a computational experiment using
molecular docking, pharmacophore filtering, and structural clustering allied to molecular dynamics
(MD) simulations and binding free energy calculations to explore the inhibitory activity of
new triterpenoids against Pin1 structure.
Results: Here, we report different computational evidence that triterpenoids from neem (Azadirachta
indica A. Juss), such as 6-deacetylnimbinene, 6-Oacetylnimbandiol, and nimbolide, replicate
the binding mode of the Pin1 substrate peptide, interacting with high affinity with the binding
site and thus destabilizing the Pin1 structure.
Conclusions: Our results are supported by experimental data, and provide interesting structural insights
into their molecular mechanism of action, indicating that their structural scaffolds could be
used as a start point to develop new inhibitors against Pin1.