Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10400.8/4981 |
Resumo: | UID/ MAR/04292/2013 |
| id |
RCAP_6cc9bc1319a9aec1f1e6b4b40cf281eb |
|---|---|
| oai_identifier_str |
oai:iconline.ipleiria.pt:10400.8/4981 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository_id_str |
7160 |
| spelling |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinonesDesigner-drugsCathinonesNMRHepatotoxicityMembrane permeabilityDeprotonationUID/ MAR/04292/2013Acknowledgments : The authors acknowledge financial support from Fundação para a Ciência e a Tecnologia through grant SFRH/BPD/110491/2015, and projects UID/Multi/04046/2013, UID/MULTI/00612/2013, UID/MAR/04292/2013 and PTDC/QEQ-COM/5904/2014. This work was done within the scope of the protocol established between FCUL, the Forensic Science Laboratory from Portuguese Criminal Police and FFUP. The authors wish to thank Mariana Pereira, Joana Alegre and Andreia Alexandre for the technical lab support at Laboratório de Polícia Científica da Polícia JudiciáriaThe emergence of potentially dangerous new psychoactive substances (NPS) imposes enormous challenges on forensic laboratories regarding their rapid and unambiguous identification. Access to comprehensive databases is essential for a quick characterization of these substances, allowing them to be categorized according to national and international legislations. In this work, it is reported the synthesis and structural characterization by NMR and MS of a library encompassing 21 cathinones, 4 of which are not yet reported in the literature, but with structural characteristics that make them a target for clandestine laboratories. This in-house library will be an important tool accessible to forensic laboratories, for the quick identification of seized NPS. The in vitro cytotoxicity of all cathinones was assessed in HepG2 cells, to have a preliminary but effective indication of their human hepatotoxicity potential. The two new cathinones DMB (8) and DMP (9) were the more cytotoxic, followed by the already seized mephedrone (2), 3,4-DMMC (3), 4-MDMC (7), NEB (12) with EC50 values ranging from 0.81 mM for (3) to 1.28 mM for (2). Results suggest an increase of cytotoxicity with the increase of the chain length of the acyl moiety and with the substitution (with one or two methyl groups) in the aromatic ring. The nature of the amine moiety seems to play only a minor role in the cytotoxic effect. Molecular dynamics simulations were performed to evaluate the molecular details related with the observed cytotoxicities. Although these studies indicated that cathinones are able to cross lipid bilayers with relative ease, when in their neutral forms, it was observed only a partial correlation between lipophilicity and cytotoxicity, indicating that membrane trafficking may not be the only key factor influencing the bioactivity of these compounds. This work is a valuable contribution to the forensic science field since a quick identification of novel cathinones is urgent to match their rapid increase in the market.ElsevierIC-OnlineGaspar, HelenaBronze, SoraiaOliveira, CatarinaVictor, Bruno L.Machuqueiro, MiguelPacheco, RitaCaldeira, Maria JoãoSantos, Susana2020-07-01T15:49:07Z20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.8/4981engGaspar, H., Bronze, S., Oliveira, C., Victor, B. L., Machuqueiro, M., Pacheco, R., Caldeira, M. J., & Santos, S. (2018). Proactive response to tackle the threat of emerging drugs: Synthesis and toxicity evaluation of new cathinones. Forensic science international, 290, 146–156. https://doi.org/10.1016/j.forsciint.2018.07.0010379-073810.1016/j.forsciint.2018.07.001metadata 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:RCAAP2024-01-17T15:50:23Zoai:iconline.ipleiria.pt:10400.8/4981Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:48:41.366193Repositório 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 |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones |
| title |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones |
| spellingShingle |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones Gaspar, Helena Designer-drugs Cathinones NMR Hepatotoxicity Membrane permeability Deprotonation |
| title_short |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones |
| title_full |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones |
| title_fullStr |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones |
| title_full_unstemmed |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones |
| title_sort |
Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones |
| author |
Gaspar, Helena |
| author_facet |
Gaspar, Helena Bronze, Soraia Oliveira, Catarina Victor, Bruno L. Machuqueiro, Miguel Pacheco, Rita Caldeira, Maria João Santos, Susana |
| author_role |
author |
| author2 |
Bronze, Soraia Oliveira, Catarina Victor, Bruno L. Machuqueiro, Miguel Pacheco, Rita Caldeira, Maria João Santos, Susana |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
IC-Online |
| dc.contributor.author.fl_str_mv |
Gaspar, Helena Bronze, Soraia Oliveira, Catarina Victor, Bruno L. Machuqueiro, Miguel Pacheco, Rita Caldeira, Maria João Santos, Susana |
| dc.subject.por.fl_str_mv |
Designer-drugs Cathinones NMR Hepatotoxicity Membrane permeability Deprotonation |
| topic |
Designer-drugs Cathinones NMR Hepatotoxicity Membrane permeability Deprotonation |
| description |
UID/ MAR/04292/2013 |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z 2020-07-01T15:49:07Z |
| 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/10400.8/4981 |
| url |
http://hdl.handle.net/10400.8/4981 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Gaspar, H., Bronze, S., Oliveira, C., Victor, B. L., Machuqueiro, M., Pacheco, R., Caldeira, M. J., & Santos, S. (2018). Proactive response to tackle the threat of emerging drugs: Synthesis and toxicity evaluation of new cathinones. Forensic science international, 290, 146–156. https://doi.org/10.1016/j.forsciint.2018.07.001 0379-0738 10.1016/j.forsciint.2018.07.001 |
| dc.rights.driver.fl_str_mv |
metadata only access info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
metadata only access |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
| instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| 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 |
| repository.mail.fl_str_mv |
|
| _version_ |
1799136980667203584 |