Design, synthesis, and biological evaluation of oxindole derivatives as antidepressive agents

• Published in: Bioorganic & medicinal chemistry letters 2015-11, Vol.25 (22), p.5281-5285
• Main Authors: Suthar, Sharad Kumar, Bansal, Sumit, Alam, Md. Maqusood, Jaiswal, Varun, Tiwari, Amit, Chaudhary, Anil, Alex, Angel Treasa, Joseph, Alex
• Format: Article
• Language: English
• Subjects: Animals; Antidepressant activity; Antidepressive Agents - chemical synthesis; Antidepressive Agents - chemistry; Antidepressive Agents - pharmacology; Benzylidene Compounds - chemical synthesis; Benzylidene Compounds - chemistry; Benzylidene Compounds - pharmacology; Clorgyline - pharmacology; Forced swimming test; Imipramine - pharmacology; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Lactams - chemical synthesis; Lactams - chemistry; Lactams - pharmacology; MAO-A inhibitors; Mice; Moclobemide - pharmacology; Molecular Docking Simulation; Monoamine Oxidase - metabolism; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; Oxindole derivatives; Structure-Activity Relationship; Tail suspension test
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.09.048

[Display omitted] The 3-substituted oxindole derivatives were designed, synthesized, and evaluated for antidepressant activity by employing forced swimming test, tail suspension test, and MAO-A inhibition assay. Results of biological studies revealed that the majority of compounds exhibited potent to moderately potent activity and among them, 12 displayed potency comparable to that of the imipramine with %DID of 37.95 and 44.84 in the FST and TST, respectively. At the same time, imipramine showed %DID of 43.62 and 50.64 in the FST and TST, correspondingly. In the MAO-A inhibition assay, 12 showed an IC50 of 18.27μmol, whereas the reference drug moclobemide displayed an IC50 of 13.1μmol. The SAR study disclosed that the presence of bromo atom at the phenyl/furanyl or thienyl moiety in the oxindole derivatives was critical for the antidepressant activity.