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Proactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinones

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dc.contributor.authorGaspar, Helena
dc.contributor.authorBronze, Soraia
dc.contributor.authorOliveira, Catarina
dc.contributor.authorVictor, Bruno L.
dc.contributor.authorMachuqueiro, Miguel
dc.contributor.authorPacheco, Rita
dc.contributor.authorCaldeira, Maria João
dc.contributor.authorSantos, Susana
dc.date.accessioned2020-07-01T15:49:07Z
dc.date.available2020-07-01T15:49:07Z
dc.date.issued2018
dc.descriptionUID/ MAR/04292/2013pt_PT
dc.descriptionAcknowledgments : 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 Judiciáriapt_PT
dc.description.abstractThe 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGaspar, 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.2018.07.001pt_PT
dc.identifier.doi10.1016/j.forsciint.2018.07.001pt_PT
dc.identifier.issn0379-0738
dc.identifier.urihttp://hdl.handle.net/10400.8/4981
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationDesenvolvimento de um novo campo de forças para lípidos baseado no GROMOS 54A7
dc.relationMARE - Marine and Environmental Sciences Centre
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectDesigner-drugspt_PT
dc.subjectCathinonespt_PT
dc.subjectNMRpt_PT
dc.subjectHepatotoxicitypt_PT
dc.subjectMembrane permeabilitypt_PT
dc.subjectDeprotonationpt_PT
dc.titleProactive response to tackle the threat of emerging drugs: synthesis and toxicity evaluation of new cathinonespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDesenvolvimento de um novo campo de forças para lípidos baseado no GROMOS 54A7
oaire.awardTitleMARE - Marine and Environmental Sciences Centre
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F110491%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04046%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F00612%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQEQ-COM%2F5904%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMAR%2F04292%2F2013/PT
oaire.citation.endPage156pt_PT
oaire.citation.startPage146pt_PT
oaire.citation.titleForensic Science Internationalpt_PT
oaire.citation.volume290pt_PT
oaire.fundingStreamOE
oaire.fundingStream5876
oaire.fundingStream5876
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameGuerreiro Galla Gaspar
person.givenNameHelena Margarida
person.identifierE-6798-2012
person.identifier.ciencia-id761C-044C-995B
person.identifier.orcid0000-0002-1613-7023
person.identifier.scopus-author-id7003891380
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project.funder.nameFundação para a Ciência e a Tecnologia
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rcaap.rightsclosedAccesspt_PT
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