Title:In Silico Study Examining New Phenylpropanoids Targets with Antidepressant Activity
Volume: 22
Issue: 5
Author(s): Poliane da Silva Calixto, Reinaldo Nóbrega de Almeida, Mirian G.S. Stiebbe Salvadori, Mayara dos Santos Maia, José Maria Barbosa Filho, Marcus Tullius Scotti and Luciana Scotti*
Affiliation:
- Laboratory of Chemoinformatics, Federal University of Paraiba, Joao Pessoa,Brazil
Keywords:
4-allyl-2, 6-dimethoxyphenol, chemoinformatics, antidepressive, toxicity, target, docking.
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: An in silico molecular modeling study, based on homology, was conducted
to determine the three-dimensional structure of the 5-hydroxytryptamine 2A receptor (5-
HT2AR), then molecular docking studies were performed and the predisposition for cytotoxicity
risk among identified molecules was examined. A model for 5-HT2AR homology, with satisfactory
results, was obtained 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.
