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  3. Design, synthesis, and biological evaluation of THIQ as antidepressive agents

Design, synthesis, and biological evaluation of THIQ as antidepressive agents

  • Bioorg Med Chem Lett. 2023 Sep 7;95:129470. doi: 10.1016/j.bmcl.2023.129470.
Xiaopeng Wei 1,  Man Zhang 1,  Yijing Guo 1,  Qianqian Chang 1,  Wei Qiao 2
Affiliations

Affiliations

  • 1 Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, PR China.
  • 2 Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, PR China. Electronic address: qiaowei@tmu.edu.cn.
PMID: 37689215 DOI: 10.1016/j.bmcl.2023.129470
Abstract

7-substituted tetrahydroisoquinolines derivatives were designed, synthesized, and evaluated for neuroprotective properties. We summarized the preliminary structure activity relationships (SAR). Compound 3i was screened as a hit compound and its antidepressant activity was evaluated by employing the forced swimming test, tail suspension test. Additionally, ADMET profile (absorption, distribution, metabolism, excretion and toxicity properties) of the compound 3i was predicted in order to evaluate their lead-like properties and safety. The interaction of compound 3i bound to MAO-A was explored using molecular docking and molecular dynamics simulation. Results of biological studies revealed that the compound 3i exhibited almost equal antidepressant activity compared with magnoflorine. Compound 3i is predicted to possess good drug like properties and safety based on ADMET profile predictions. This work provides ideas for the drugs discovery of antidepressant agents.

Keywords

Antidepressants; Forced swimming test; Molecular docking; Molecular dynamics simulation; Tail suspension test; Tetrahydroisoquinolines (THIQ).

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