Design, Synthesis and Evaluation of the Antidepressant and Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles

Title:Design, Synthesis and Evaluation of the Antidepressant and Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles

Volume: 16 Issue: 2

Author(s): Ming-Xia Song, Bao-Qi Rao, Bin-Bin Cheng, Wu Yi, Hong Zeng, You-gen Luo and Xian-Qing Deng

Affiliation:

Keywords: Antidepressant, anticonvulsant, benzo[d]oxazole, triazole, forced swimming test, maximal electroshock.

Abstract: Background: Epilepsy and depression are two of the common diseases seriously threatening life and health of human. A shared neurobiological substrate led to the bidirectional relationship and high comorbid occurrence of the two disorders. Recently, an increasing number of patients with epilepsy (PWE) require some form of antidepressant medication. However, most of the available antidepressants are inadequate for PWE for some reasons. So, the search for novel and increasingly effective drugs with anticonvulsant and antidepressant activities is necessary.

Methods: A series of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles (5a-p) were designed and synthesized. Their anticonvulsant activities were evaluated using maximal electroshock shock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. Their antidepressant activities were screened with the forced swimming test (FST).

Results: All the compounds showed anti-MES activities in different degree, among which 5g and 5j were the most promising one with ED50 value of 31.7 and 12.7 mg/kg, respectively. What’s more, 5g and 5j also exhibited nice anti-scPTZ activities and low neurotoxicity. Interestingly, these compounds also showed good antidepressant activities in FST. And the efficacy of 5g were also confirmed by a tail suspension test and a open field test. The pretreatment of thiosemicarbazide (an inhibitor of γ- aminobutyric acid synthesis enzyme) significantly increased the ED50 of 5g in MES and reversed the reductions in the immobility time of 5g in FST.

Conclusion: Triazole-containing benzo[d]oxazole is a good skeleton to develop compounds with both anticonvulsant and antidepressant activities. We have got the compound 5g, which display remarkable antidepressant and anticonvulsant activities, and the GABAergic system was involved in the action mechanism of 5g.

Cite this article as:

Song Ming-Xia, Rao Bao-Qi, Cheng Bin-Bin, Yi Wu, Zeng Hong, Luo You-gen and Deng Xian-Qing, Design, Synthesis and Evaluation of the Antidepressant and Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles, CNS & Neurological Disorders - Drug Targets 2017; 16 (2) . https://dx.doi.org/10.2174/1871527315666160822112501

DOI https://dx.doi.org/10.2174/1871527315666160822112501	Print ISSN 1871-5273
Publisher Name Bentham Science Publisher	Online ISSN 1996-3181