Antidepressant-like Effect of 1-(2-(4-(4-Ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one in Mice: Evidence of the Contribution of the Serotonergic System

Abstract

Major depressive disorder (MDD) is a psychiatric disorder that affects a large portion of the population, with dysregulation of the serotonergic system, which is deeply involved in both the pathophysiology of MDD and mechanism of action of many antidepressants. Current pharmacological therapies do not meet the neurobiological needs of all depressed individuals, making the development of new antidepressants necessary. In recent decades, compounds containing triazoles have become promising due to their range of biological activities, including antidepressant activity. In this study, we evaluated the antidepressant-like effect of a hybrid containing triazole and acetophenone, 1-(2-(4-(4ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one (ETAP) (0.5−5 mg/kg), in the forced swimming test (FST) and tail suspension test (TST) in mice, as well as the involvement of the serotonergic system in this effect. Our findings demonstrated that ETAP exhibited an antidepressant-like effect from the dose of 1 mg/kg and that this effect is modulated by 5-HT 2A/2C and 5-HT 4 receptors. We also demonstrated that this effect may be related to inhibition of monoamine oxidase A activity in the hippocampus. Additionally, we evaluated the in silico pharmacokinetic profile of ETAP, which predicted its penetration into the central nervous system. ETAP exhibited a low potential for toxicity at a high dose, making this molecule interesting for the development of a new therapeutic strategy for MDD.

Organocatalytic Synthesis and DNA Interactive Studies of New 1,2,3‐triazolyl‐thiazolidines Hybrids

“…[26][27][28] In recent years, our research group has focused on the synthesis of novel molecules containing the 1,2,3-triazole unit and assessing their biological properties to explore new avenues for their utilization. [29][30][31][32][33][34] According to the literature, in addition to the broad pharmacological applications of thiazolidines, combining them with other classes of molecules with established properties leads to the creation of intriguing hybrid derivatives. Examples include thiazole-thiazolidinedione hybrids, [35] spirothiazolidines, [36] and thiazolidinone Cu(II) and Fe(III) complexes designed to investigate interactions with DNA and serum albumins.…”