Interaction models of the protein Phosphoethanolamine Methyltransferase from Haemonchus contortus relating drugs and lignans through molecular docking

Alternatives to the use of synthetic anthelmintics to control parasitosis in sheep, mainly caused by the nematode Haemonchus contortus, have been studied, among them, the use of natural products 1. In vitro studies with the cubebin, dihydrocubebin and hinokinin, lignans isolated from Piper cubeba, against eggs and different larval stages of H. contortus demonstrated the action of these lignans, with hinokinin being the most effective (IC50 <70 μg / mL) without differences with the albendazole control. Molecular docking studies of lignans and albendazole (as an interaction model) were performed using Phosphoethanolamine methyltransferases (PDB 4KRG), which acts on the synthesis of the cell membrane of the nematode. The consensual docking study used the Maestro 10.1 and GOLD 5.1 softwares. The results of the overlap of the poses (fig.1) obtained from albendazole and lignans showed that they occupy the same region of the active site of protein. Cubebin presented a different interaction model of albendazole, presenting in common the hydrophobic interaction with Leu124. The hinokinin presented an interaction model similar to albendazole with hydrophobic interaction Phe81, Leu124 and hydrogen bonding Asp105, as well as dihydrocubebin with hydrophobic interaction with Phe81, Leu124 and hydrogen bonding with Asn124. These results demonstrate that the in vitro action of these two lignans may be related to the deactivation of this enzyme according to the model of interaction of albendazole.