Synthesis and Evaluation of Antidepressant Activities of 5-Aryl-4,5-dihydrotetrazolo [1,5-]thieno[2,3-]pyridine Derivatives.

Abstract

In this study, we synthetized a series of 5-aryl-4,5-dihydrotetrazolo[1,5-]thieno[2,3-]pyridine derivatives containing tetrazole and other heterocycle substituents, i.e., triazole, methyltriazole, and triazolone. The forced swim test (FST) and tail suspension test (TST) were used to evaluate the antidepressant activity of the target compounds. The compound 5-[4-(trifluoromethyl)phenyl]-4,5-dihydrotetrazolo[1,5-]thieno[2,3-]pyridine () showed the highest antidepressant activity, with a reduced immobility time of 55.33% when compared with the control group. Using an open-field test, compoundwas shown to not affect spontaneous activity of mice. The determination of in vivo 5-hydroxytryptamine (5-HT) concentration showed that compoundmay have an effect in the mouse brain. The biological activities of all synthetized compounds were verified by molecular docking studies. Compoundshowed significant interactions with residues of the 5-HTreceptor homology model.