Evaluation of Potential Anxiolytic Activity of TRPV1 Antagonists Using Pharmacophore-Based Virtual Screening

The sharp increase in individuals suffering from an anxiety disorder has caused some concern, since people cannot be as productive as in the past, thus affecting different interpersonal relationships and execution of different activities. In view of this, it is relevant to carry out research focused on therapeutic innovations for the treatment of anxiety disorders, as a way to develop pharmaceutical products with greater therapeutic efficacy and fewer side effects. The objective is, therefore, to evaluate the therapeutic potential of molecules with activity in the TRVP1 receptor for the treatment of generalized anxiety disorder, through studies on the structure–activity relationship. For this purpose, a virtual screening was performed based on the derivation of the pharmacophore of TRVP1 antagonist molecules, described in the literature with the respective IC50 values. From this initial screening, molecules with similar pharmacophoric patterns and their different conformers were then sought, so that specific filters could be applied. These molecular filters consisted of relating the structures through the similarity of 3D shape, electronic characteristics and pharmacokinetic/toxicological patterns with orally administered drugs. The compounds that were not retained on the applied filters were then studied for analysis of the relationship between the interaction with the TRPV1 receptor, through molecular consensus docking. After screening, based on the use of such methods, two molecules with potential activity in TRPV1 were obtained in the end, with excellent prediction of toxicity, with no structural alert, in addition to presenting a favorable pharmacokinetic prediction for a drug with action at the central level for oral use.