Molecular docking study of Acmella oleracea alkylamides

Acmella oleracea, popularly known as jambu, is a naturalized species in Brazil. In the northern region of Brazil, where it is widely cultivated, the species is used in cooking and folk medicine (Poltronieri, Muller e Poltronieri, 2000). The chemical marker of the species is the alkylamide known as spilanthol, an N-isobutyl-2E, 6Z, 8E-decatrienamide, which has many applications in the pharmaceutical setting such as larvicidal, fungicidal and antimicrobial properties, in addition to its anesthetic effect (Barbosa et al. 2016). Besides spilanthol other alkylamides have already been described for the species by our research group (Simas, et al. 2013). Given the potential of this substance, this paper seeks to study the structure-activity relationship of alkylamides with the endocannabinoid system. It is known that these substances can interact with cannabinoid receptors inferring an anti-inflammatory response. Six alkylamides, including spilanthol, were selected for in silico analysis. Molecular docking of the ligands was performed with Auto Dock Vina software on the active CB1 and CB2 receptor obtained from Protein Data Bank (PDB) code 5TGZ and 5ZTY, respectively. The agonist structures of each receptor and the alkylamides of interest for docking were quantum-optimized in the Gaussian 09 software. The obtained complexes, protein and ligand, were analyzed in the Discovery Studio Visualizer version 2019 Client software for energy and interactions analysis. The results for each receptor (CB1 and CB2) show that alkylamides are molecules with a great potential to interact with these receptors and may have some therapeutic activity in the endocannabinoid system. Spilanthol had a better interaction with protein CB1 with an energy of -7.6 kcal mol-1 (comparing the energy of the CB1 receptor agonist -8,2 kcal mol-1) versus -7.3 kcal mol-1 for the CB2 receptor (comparing the energy of the CB2 receptor agonist -8,1 kcal mol-1). In general, the action of alkylamides on the CB1 receptor would not be interesting because of the effects on the central nervous system, where we find this receptor mostly. Thus, further analysis is necessary to verify that these molecules can reach CB1 receptors and have any undesired effect.