Molecular Docking of Azadirachtin in Nuclear Ecdysone Receptor

Abstract

Background: The azadirachtin is a triterpenoid associated with growth inhibition in several kinds of insects which cause epidemic diseases like Dengue, Chikungunya and Malaria. Azadirachtin acts by inhibiting the Ecdysone Receptor (EcR), which is responsible from larvae phase in insects. However, the interaction between the azadirachtin molecule and the Ecdysone Receptor is unknown. In this work, we used the program Dock Thor to generate several azadirachtin conformations inside the EcR binding site. The ten most stable conformations were optimized with the ONIOM approach present in the Gaussian 09 program. The interaction energy was calculated between the azadirachtin molecule and EcR receptor. Theoretical calculation shows that the azadirachtin molecule interacts with the same amino acids present in the ecdysone EcR interaction. These results will be useful to design new EcR inhibitors, which can be used in the control of some diseases based on insect proliferations. Objective: To understand the interaction between the natural insecticide azadirachtin and the Ecdysone Receptor. Methods: A combination of Dock Thor program with QM-MM calculation was used in order to obtain the most favorable molecular structures. Results: The hydrogens bond obtained by Dock Thor Program combined with QM-MM calculation suggest the azadirachtin interact with EcR in the same way that ecdysone molecule. Conclusion: The interaction mode that the molecule azadirachtin inhibits EcR in order to avoid insect proliferation was described. A R T I C L E H I S T O R Y Received: December 29, 2018 Revised: January 28, 2019 Accepted: March 08, 2019 DOI: 10.2174/1877946809666190320141833