Evaluation of Neurotoxicity of NBOH Derivatives
Rodrigo Foss da Silva, Lennon Machado Alves, Fernanda Conte, Bruno Pereira Dos Santos, Rodrigo Ligabue‐braun, Solange Cristina García, Tiago Franco de Oliveira, Hecson Jesser Segat, Silvana Peterini Boeira, Dieniffer Espinosa Janner, Ana Cristina Correa Carvalhal Ferreira, Ariane Correa Carvalhal Ferreira, Marcelo Dutra Arbo
Pharmaceuticals July 8, 2026 DOI: 10.3390/ph19071055 via OpenAlex
Summary
AI-generated from the abstractNBOHs, a class of new psychoactive substances acting on serotonin receptors, show varying neurotoxicity. In human neuron-like cells, two derivatives, 25E-NBOH and 25B-NBOH, reduced cell viability, caused mitochondrial hyperpolarization, and increased oxidative species. In fruit flies, 25B-NBOH impaired climbing ability, and both 25E-NBOH and 25B-NBOH elevated catalase and acetylcholinesterase enzyme activities at 50 nM. These results suggest that 25E- and 25B-NBOH are more toxic than 25I-NBOH, with potential mechanisms involving mitochondrial signaling, oxidative stress, and cholinergic disruption.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Differentiated SH-SY5Y cells and Drosophila melanogaster |
| Keywords | Neurotoxicity Viability assay Oxidative stress Aché Mitochondrion |
| Key finding | 25E-NBOH and 25B-NBOH decreased cell viability, induced mitochondrial hyperpolarization and oxidative stress in cells, and increased catalase and acetylcholinesterase activities in flies, indicating greater neurotoxicity than 25I-NBOH. |
Abstract
Background/Objectives: The study sought to investigate the neurotoxicity of NBOHs, which are a class of new psychoactive substances (NPSs) that act as agonists of serotonin 5-HT2A and 5-HT2C receptors, resulting in hallucinogenic effects similar to those of LSD, often found in paper blotters. Methods: Differentiated SH-SY5Y cells were incubated for 24 h with 0.5, 1.0, 3.5, 5 and 10 nM of the derivatives 25I-NBOH, 25E-NBOH and 25B-NBOH. Cell viability was assessed by MTT reduction and neutral red uptake assays. Mitochondrial membrane potential and production of free radicals were also evaluated. In addition, Drosophila melanogaster flies were exposed to 5, 10 and 50 nM of each NBOH derivative for 4 h. Negative geotaxis, CAT, and AChE enzymatic activities were evaluated. Results: Both 25E-NBOH and 25B-NBOH decreased cell viability. Furthermore, mitochondrial hyperpolarization of cells and an increase in oxidative species were observed in response to higher concentrations of 25E-NBOH and 25B-NBOH. In D. melanogaster, 25B-NBOH increased climbing time and both 25E-NBOH and 25B-NBOH increased CAT and AChE activities at 50 nM. Conclusions: These findings indicate greater toxicity of the 25E- and 25B-NBOH compared to 25I-NBOH, suggesting metabolic activity or mitochondrial signaling, oxidative stress, and cholinergic dysregulation as a potential mechanism related to NBOH neurotoxicity.