Publication
Synthesis, Characterization, and Biological Effects of Chloro-Cathinones: Toxicity and Potential Neurological Impact
| datacite.subject.sdg | 12:Produção e Consumo Sustentáveis | |
| datacite.subject.sdg | 13:Ação Climática | |
| datacite.subject.sdg | 14:Proteger a Vida Marinha | |
| dc.contributor.author | Gomes, Ana Patrícia | |
| dc.contributor.author | Ferro, Raquel | |
| dc.contributor.author | Pinto, Daniela | |
| dc.contributor.author | Silva, Joana | |
| dc.contributor.author | Alves, Celso | |
| dc.contributor.author | Pacheco, Rita | |
| dc.contributor.author | Gaspar, Helena | |
| dc.date.accessioned | 2025-07-04T09:45:47Z | |
| dc.date.available | 2025-07-04T09:45:47Z | |
| dc.date.issued | 2025-04-09 | |
| dc.description.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. | eng |
| dc.description.sponsorship | This work was funded by the Portuguese Foundation for Science and Technology (FCT) through the following projects: BioISI-BioSystems and Integrative Sciences Institute UID/00100, BioISI (DOI: https://doi.org/10.54499/UIDB/04046/2020); MARE—Marine and Environmental Sciences Centre UIDP/04292/2020 (DOI: https://doi.org/10.54499/UIDP/04292/2020) and UIDB/04292/2020 (DOI: https://doi.org/10.54499/UIDB/04292/2020); Associate Laboratory ARNET (LA/P/0069/2020—https://doi.org/10.54499/LA/P/0069/2020). The FCT also funded this work through the project NEURONS4—New edge in the therapeutics of Parkinson’s disease from seaweeds 2022.09196.PTDC (DOI: https://doi.org/10.54499/2022.09196.PTDC). This research was also financed by Centro de Química Estrutural, a Research Unit (RU) funded by the FCT, projects UIDB/00100/2020 (DOI: https://doi.org/10.54499/UIDB/00100/2020) and UIDP/00100/2020 (DOI: https://doi.org/10.54499/UIDP/00100/2020). The Institute of Molecular Sciences is an Associate Laboratory funded by the FCT, project LA/P/0056/2020 (DOI: https://doi.org/10.54499/LA/P/0056/2020). FCT also provided funding through grants EECINST/00060/2021/CP2902/CT0004 (C. Alves, https://doi.org/10.54499/CEECINST/00060/2021/CP2902/CT0004) and 2023.06590.CEECIND (J. Silva, https://doi.org/10.54499/2023.06590.CEECIND/CP2852/CT0002)). | |
| dc.identifier.citation | Gomes, A.P.; Ferro, R.; Pinto, D.; Silva, J.; Alves, C.; Pacheco, R.; Gaspar, H. Synthesis, Characterization, and Biological Effects of Chloro-Cathinones: Toxicity and Potential Neurological Impact. Int. J. Mol. Sci. 2025, 26, 3540. https:// doi.org/10.3390/ijms26083540 | |
| dc.identifier.doi | 10.3390/ijms26083540 | |
| dc.identifier.issn | 1422-0067 | |
| dc.identifier.uri | http://hdl.handle.net/10400.8/13529 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.publisher | MDPI AG | |
| dc.relation | Biosystems and Integrative Sciences Institute | |
| dc.relation | Marine and Environmental Sciences Centre | |
| dc.relation.hasversion | https://www.mdpi.com/1422-0067/26/8/3540 | |
| dc.relation.ispartof | International Journal of Molecular Sciences | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | NPS | |
| dc.subject | cathinones | |
| dc.subject | NMR | |
| dc.subject | GC-MS | |
| dc.subject | HRMS | |
| dc.subject | SH-SY5Y | |
| dc.subject | acetylcholinesterase | |
| dc.title | Synthesis, Characterization, and Biological Effects of Chloro-Cathinones: Toxicity and Potential Neurological Impact | eng |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Biosystems and Integrative Sciences Institute | |
| oaire.awardTitle | Marine and Environmental Sciences Centre | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04046%2F2020/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04292%2F2020/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Base/UIDB%2F04292%2F2020/PT | |
| oaire.citation.issue | 8 | |
| oaire.citation.startPage | 1 | |
| oaire.citation.title | International Journal of Molecular Sciences | |
| oaire.citation.volume | 26 | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| oaire.fundingStream | 6817 - DCRRNI ID | |
| oaire.fundingStream | Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Base | |
| oaire.version | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |
| person.familyName | Silva | |
| person.familyName | Alves | |
| person.givenName | Joana | |
| person.givenName | Celso | |
| person.identifier | 98885 | |
| person.identifier | 159091 | |
| person.identifier.ciencia-id | 6317-6F15-BA35 | |
| person.identifier.ciencia-id | 501C-F268-2E60 | |
| person.identifier.orcid | 0000-0003-1224-1699 | |
| person.identifier.orcid | 0000-0003-1581-2127 | |
| person.identifier.rid | B-3366-2017 | |
| person.identifier.scopus-author-id | 56370819800 | |
| person.identifier.scopus-author-id | 55654969100 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
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