Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells

Detalhes bibliográficos
Autor(a) principal: Soares, Jorge
Data de Publicação: 2019
Outros Autores: Costa, Vera Marisa, Gaspar, Helena, Santos, Susana, Bastos, Maria de Lourdes, Carvalho, Félix, Capela, João Paulo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.8/5102
Resumo: Jorge Soares acknowledges University of Porto/Faculty of Medicine University of Porto through FSE - Fundo Social Europeu, NORTE2020 - Programa Operacional Regional do Norte for his grant (NORTE-08-5369-FSE-000011). This work received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007728) and National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/MULTI/04378/2013 (UCIBIO), UID/MULTI/00612/2013 (CQB), UID/MAR/04292/2013 (MARE) and UID/Multi/04046/2013 (BioISI). Also supported by the project NORTE-01-0145-FEDER000024, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement (DESignBIOtecHealth—New Technologies for three Health Challenges of Modern Societies: Diabetes, Drug Abuse and Kidney Diseases), through the European Regional Development Fund (ERDF). Vera Marisa Costa acknowledges Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015). The authors wish to thank the Laboratório de Polícia Científica da Polícia Judiciária (LPC-PJ) for providing the smartshop products within the scope of the protocol established between LPC-PJ, FCUL and FFUP.
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spelling Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cellsSynthetic cathinonesClassical amphetaminesCytotoxicitySH-SY5Y cellsStructure-toxicity relationshipJorge Soares acknowledges University of Porto/Faculty of Medicine University of Porto through FSE - Fundo Social Europeu, NORTE2020 - Programa Operacional Regional do Norte for his grant (NORTE-08-5369-FSE-000011). This work received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007728) and National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/MULTI/04378/2013 (UCIBIO), UID/MULTI/00612/2013 (CQB), UID/MAR/04292/2013 (MARE) and UID/Multi/04046/2013 (BioISI). Also supported by the project NORTE-01-0145-FEDER000024, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement (DESignBIOtecHealth—New Technologies for three Health Challenges of Modern Societies: Diabetes, Drug Abuse and Kidney Diseases), through the European Regional Development Fund (ERDF). Vera Marisa Costa acknowledges Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015). The authors wish to thank the Laboratório de Polícia Científica da Polícia Judiciária (LPC-PJ) for providing the smartshop products within the scope of the protocol established between LPC-PJ, FCUL and FFUP.Synthetic cathinones also known as β-keto amphetamines are a new group of recreational designer drugs. We aimed to evaluate the cytotoxic potential of thirteen cathinones lacking the methylenedioxy ring and establish a putative structure-toxicity profile using differentiated SH-SY5Y cells, as well as to compare their toxicity to that of amphetamine (AMPH) and methamphetamine (METH). Cytotoxicity assays [mitochondrial 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction and lysosomal neutral red (NR) uptake] performed after a 24-h or a 48-h exposure revealed for all tested drugs a concentration-dependent toxicity. The rank order regarding the concentration that promoted 50 % of toxicity, at 24 h exposure, by the MTT assay was: 3,4-dimethylmethcathinone (3,4-DMMC)>METH > mephedrone ≈ α-pyrrolidinopentiophenone > AMPH ≈ methedrone > pentedrone > buphedrone ≈ flephedrone>α-pyrrolidinobutiophenone > methcathinone ≈ N-ethylcathinone>α-pyrrolidinopropiophenone>N,N-dimethylcathinone ≈ amfepramone. Apoptotic cell death signs were seen for all studied cathinones. 3,4-DMMC, methcathinone and pentedrone triggered autophagy activation, as well as increased reactive oxygen species production, and N-acetyl-L-cysteine (NAC) totally prevented that rise. Importantly, NAC was also able to prevent the cytotoxicity promoted by 6 tested drugs, ruling for an involvement of oxidative stress in the toxic events observed. The increased lipophilic chain on the alpha carbon, the presence and the high steric volume occupied by the substituents on the aromatic ring, and the substitution of the pyrrolidine ring by its secondary amine analogue have proved to be key points for the cytotoxicity profile of these cathinones. The structure-toxicity relationship established herein may enlighten future human relevant mechanistic studies, and future clinical approaches on intoxications.ElsevierIC-OnlineSoares, JorgeCosta, Vera MarisaGaspar, HelenaSantos, SusanaBastos, Maria de LourdesCarvalho, FélixCapela, João Paulo2020-08-19T13:54:14Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.8/5102engSoares, J., Costa, V. M., Gaspar, H., Santos, S., Bastos, M.L., Carvalho, F., & Capela, J. P. (2019). Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells. Neurotoxicology, 75, 158–173. https://doi.org/10.1016/j.neuro.2019.08.0090161-813X10.1016/j.neuro.2019.08.009metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-17T15:50:34Zoai:iconline.ipleiria.pt:10400.8/5102Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:48:45.616425Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells
title Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells
spellingShingle Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells
Soares, Jorge
Synthetic cathinones
Classical amphetamines
Cytotoxicity
SH-SY5Y cells
Structure-toxicity relationship
title_short Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells
title_full Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells
title_fullStr Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells
title_full_unstemmed Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells
title_sort Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells
author Soares, Jorge
author_facet Soares, Jorge
Costa, Vera Marisa
Gaspar, Helena
Santos, Susana
Bastos, Maria de Lourdes
Carvalho, Félix
Capela, João Paulo
author_role author
author2 Costa, Vera Marisa
Gaspar, Helena
Santos, Susana
Bastos, Maria de Lourdes
Carvalho, Félix
Capela, João Paulo
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv IC-Online
dc.contributor.author.fl_str_mv Soares, Jorge
Costa, Vera Marisa
Gaspar, Helena
Santos, Susana
Bastos, Maria de Lourdes
Carvalho, Félix
Capela, João Paulo
dc.subject.por.fl_str_mv Synthetic cathinones
Classical amphetamines
Cytotoxicity
SH-SY5Y cells
Structure-toxicity relationship
topic Synthetic cathinones
Classical amphetamines
Cytotoxicity
SH-SY5Y cells
Structure-toxicity relationship
description Jorge Soares acknowledges University of Porto/Faculty of Medicine University of Porto through FSE - Fundo Social Europeu, NORTE2020 - Programa Operacional Regional do Norte for his grant (NORTE-08-5369-FSE-000011). This work received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007728) and National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/MULTI/04378/2013 (UCIBIO), UID/MULTI/00612/2013 (CQB), UID/MAR/04292/2013 (MARE) and UID/Multi/04046/2013 (BioISI). Also supported by the project NORTE-01-0145-FEDER000024, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement (DESignBIOtecHealth—New Technologies for three Health Challenges of Modern Societies: Diabetes, Drug Abuse and Kidney Diseases), through the European Regional Development Fund (ERDF). Vera Marisa Costa acknowledges Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015). The authors wish to thank the Laboratório de Polícia Científica da Polícia Judiciária (LPC-PJ) for providing the smartshop products within the scope of the protocol established between LPC-PJ, FCUL and FFUP.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
2020-08-19T13:54:14Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.8/5102
url http://hdl.handle.net/10400.8/5102
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Soares, J., Costa, V. M., Gaspar, H., Santos, S., Bastos, M.L., Carvalho, F., & Capela, J. P. (2019). Structure-cytotoxicity relationship profile of 13 synthetic cathinones in differentiated human SH-SY5Y neuronal cells. Neurotoxicology, 75, 158–173. https://doi.org/10.1016/j.neuro.2019.08.009
0161-813X
10.1016/j.neuro.2019.08.009
dc.rights.driver.fl_str_mv metadata only access
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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