Novel piperazine-2,5-dione analogs bearing 1H-indole: Synthesis and biological effects

Abstract

In this work, a series of novel piperazine-2,5-dione derivatives bearing indole analogs (2a-2q) was designed and synthesized. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR spectroscopy, and ESI-MS. They were then evaluated for their anti-depressant, anti-inflammatory, and analgesic activities in vivo. The experimental results revealed that all the compounds showed clear anti-depressant, anti-inflammatory, and analgesic effects at a dose of 10 mg/kg. Among them, compounds 2e and 2q exhibited the best anti-depressant effects (the percent decreases in the duration of immobility were 70.2% and 71.2%, respectively), which were similar to that of fluoxetine (67.9%) in the forced swim test. Additionally, compounds 2e and 2q also displayed good anti-inflammatory and analgesic activities. Literature reports have highlighted the anti-inflammatory and analgesic effects of anti-depressant drugs, suggesting that they may have a similar mechanism of action. Therefore, further studies to investigate the possible mechanisms of action of compounds 2e and 2q are warranted.

Keywords: Analgesic; Anti-depressant; Anti-inflammatory; Indole; Piperazine-2,5-dione; Structure activity relationship.