Physicochemical stability and toxicity assessment of cimitrypazepine, an azepino[5,4,3-<i>cd</i>]indole alkaloid

Cimitrypazepine is an azepino[5,4,3-<i>cd</i>]indole alkaloid and is able to modulate CNS targets. However, there is a lack of information regarding the safety of this compound. Here, the chemical stability and toxicity of cimitrypazepine were assessed. <i>In silico</i> studies demonstrated that C-5, in the indole moiety, can undergo hydrolytic reactions; C-3, in the azepine moiety, is the most susceptible to oxidative degradation. Through <i>in vitro</i> assays, cimitrypazepine was unstable to acidic conditions, degrading by ∼50% in 3 h. Regarding toxicity, the alkaloid decreased HepG2 cells viability by 21% at 10 μM. It did not influence AST and LDH levels, but increased ALT levels. Genotoxicity, evaluated by the comet assay, was observed for concentrations above 2.5 mM. Finally, using zebrafish embryos, the LC₅₀ at 96 h post-fertilization was estimated as 326 μM. This study highlights that care must be taken regarding cimitrypazepine concentration and formulation, to avoid toxicity and degradation.