Synthesis of 1, 3, 4-oxadiazoles derivatives with antidepressant activity and their binding to the 5-HT1A receptor. Issue 51 (20th August 2020)

• Record Type: Journal Article
• Authors: Wang, Shiben; Qi, Lin; Liu, Hui; Lei, Kang; Wang, Xuekun; Liu, Renmin
• Is Part Of: RSC advances. Volume 10:Issue 51(2020)
• Page Start: 30848
• Page End: 30857
• Publication Date: 2020-08-20
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra05886f
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Compound 10g (R = –CH2 Ph ( p -Cl)) showed the best antidepressant activity in vivo and in vitro . Abstract : In this study, two series of 1, 3, 4-oxadiazole derivatives were designed and synthesized using the forced swimming test (FST) model to test the antidepressant activity of the target compound in vivo . Five compounds with potential activity were selected from the FST model to test affinity with 5-HT1A receptor in vitro . The results of the FST experiment showed that compound N -(3-((5-((4-chlorobenzyl)thio)-1, 3, 4-oxadiazol-2-yl)methoxy)phenyl)acetamide (10g ) showed the best antidepressant activity (DID = 58.93, percentage decrease in immobility duration in FST), similar to the activity of positive drug fluoxetine. Compound 10g also exhibited the most potent binding affinity to 5-HT1A receptors ( K i = 1.52 nM). The results of the in vivo 5-HT concentration estimation in mice showed that compound 10g may have an effect on the brain. The experimental results of exploratory activity in mice showed that compound 10g did not affect spontaneous activity in the open-field test model. Molecular docking was used to study the binding mode of compound 10g and the 5-HT1A receptor. Compound 10g showed significant interactions with residues at the active site on the 5-HT1A receptor. The physicochemical and pharmacokinetic properties of the target compounds were predicted using Discovery Studio 2019 and ChemBioDraw Ultra 14.