Synthesis, Characterization, and Biological Effects of Chloro-Cathinones: Toxicity and Potential Neurological Impact
Year: 2025
Type: article
Abstract: Cathinones, a class of synthetic new psychoactive substances (NPSs), continue to emerge and pose public threats. Government control efforts often lead to the emergence of new isomers, which have adverse repercussions on NPSs identification and risk prediction. This work reports on the synthesis and structural characterization of twenty chloro-cathinones, including different isomers, to create analytical data to facilitate their identification in forensic and clinical contexts. Additionally, the potential of these cathinones to cause neuronal damage was evaluated. In vitro cytotoxicity was assessed using a differentiated human neuroblastoma cell line (SH-SY5Y) as a dopaminergic neuronal model. The tested cathinones showed LC50 values from 0.6 to 2.5 mM, with 4-CBC being the most cytotoxic. The most toxic cathinones increase reactive oxygen species levels and/or cause mitochondrial membrane potential depolarization. Furthermore, this study explored, for the first time, the effect of cathinones on the cholinergic system through acetylcholinesterase (AChE) inhibition. All tested cathinones inhibited AChE with IC50 values between 0.1 and 2 mM. Molecular docking analysis revealed that the most inhibitory cathinones interacted with the CASs and PASs in AChE’s active gorge. These findings provide valuable insights into the effects of cathinones, highlighting potential health risks and structural features that may influence their toxicity towards the cholinergic system and neuronal damage.
DOI: 10.3390/ijms26083540
Authors: Ana Patrícia Gomes, Raquel Ferro, Daniela Pinto, Joana Silva, Celso Alves, Rita Pacheco, Helena Gaspar
Language: English
Subfield: Toxicology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G109349175, G1116544697, G1157612158, G1378031221, G1557386205, G1570005492, G1728218751, G2021394994, G2225939727, G2454277087, G2578531282, Centro de Química Estrutural, Rede de Infraestruturas em Investigação Aquática, Untitled, G298144591, Instituto de Ciências Moleculares, G3455070883, G3484206579, G3492720047, G3748091735, Centro de Ciências do Mar e do Ambiente, G4038499987, G4053837791, G4360740988, G4961478360, G5110214942, Instituto de Biosistemas & Ciências Integrativas, G5559457486, G5573145039, G671296436, G6997658380, G7276782832, G7480029375, Centro de Química Estrutural, G7961091540, Centro de Ciências do Mar e do Ambiente, G8809137387, G8929196965, G9000071933
OpenAlex ID: W4409313758