In Silico Study Examining New Phenylpropanoids Targets with Antidepressant Activity

Abstract

Background: Natural products, such as phenylpropanoids, which are found in essential oils derived from aromatic plants, have been explored during non-clinical psychopharmacology studies, to discover new molecules with relevant pharmacological activities in the central nervous system, especially antidepressant and anxiolytic activities. Major depressive disorder is a highly debilitating psychiatric disorder and is considered to be a disabling public health problem, worldwide, as a primary factor associated with suicide. Current clinically administered antidepressants have late-onset therapeutic actions, are associated with several side effects, and clinical studies have reported that some patients do not respond well to treatment or reach complete remission. Objective: To review important new targets for antidepressant activity and to select phenylpropanoids with antidepressant activity, using Molegro Virtual Docker and Ossis Data Warris, and to verify substances with more promising antidepressant activity. Results and Conclusion: We conducted an in silico molecular modeling study, based on homology, to determine the three-dimensional structure the 5-hydroxytryptamine 2A receptor (5-HT2AR), then performed molecular docking studies and examined the predisposition for cytotoxicity risk among identified molecules. We obtained a model for 5-HT2AR homology, with satisfactory results, indicating the good stereochemical quality of the model. The phenylpropanoid 4- allyl-2,6-dimethoxyphenol showed the lowest binding energy for 5-HT2AR, with results relevant to the L-arginine/nitric oxide (NO)/cGMP pathway, and showed no toxicity within the parameters of mutagenicity, carcinogenicity, reproductive system toxicity, and skin-tissue irritability, when evaluated in silico; therefore, this molecule can be considered promising for the investigation of antidepressant activity.

Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against Toxoplasma gondii

“…The complexed ligand was used to define the active site. The compound was then imported to analyze the stability of the system through the interactions identified with the active site of the enzyme, taking as a reference the energy value of the MolDock Score [22]. The MolDock SE (Simplex Evolution) algorithm was used with the following parameters: A total of 10 runs with a maximum of 1500 iterations, using a population of 50 individuals, with 2000 minimization steps for each flexible residual and 2000 global minimization steps per run.…”