Repository logo
 
Publication

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

2018-09Journal article Restricted access
Simple item page
dc.contributor.authorGaspar, Helena
dc.contributor.authorBronze, Soraia
dc.contributor.authorOliveira, Catarina
dc.contributor.authorVictor, Bruno
dc.contributor.authorMachuqueiro, Miguel
dc.contributor.authorPacheco, Rita
dc.contributor.authorCaldeira, Maria João
dc.contributor.authorSantos, Susana
dc.date.accessioned2018-11-28T11:21:08Z
dc.date.available2018-11-28T11:21:08Z
dc.date.issued2018-09
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, Helena; [et al] – Proactive response to tackle the threat of emerging drugs: Synthesis and toxicity evaluation of new cathinones. Forensic Science International. ISSN 0379-0738. Vol. 290 (2018), pp. 146-156pt_PT
dc.identifier.doihttps://doi.org/10.1016/j.forsciint.2018.07.001pt_PT
dc.identifier.issn0379-0738
dc.identifier.issn1872-6283
dc.identifier.urihttp://hdl.handle.net/10400.21/9098
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.relation.publisherversionhttps://reader.elsevier.com/reader/sd/pii/S0379073818303797?token=808ABA646C70219F229BB0B41031A4698FA4B0F39AB7C7F845AF746C7B9996D1FD8D73A8F73AB685ACE41C128FADD594pt_PT
dc.subjectDesigner-drugspt_PT
dc.subjectCathinonespt_PT
dc.subjectNMRpt_PT
dc.subjectHepatotoxicitypt_PT
dc.subjectMembrane permeabilitypt_PT
dc.subjectDeprotonationpt_PT
dc.subjectHepatotoxicidadept_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.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/5876/UID%2FMAR%2F04292%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQEQ-COM%2F5904%2F2014/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.fundingStream5876
oaire.fundingStream3599-PPCDT
person.familyNameGaspar
person.familyNameVictor
person.familyNameMachuqueiro
person.familyNamePacheco
person.familyNameSantos
person.givenNameHelena
person.givenNameBruno
person.givenNameMiguel
person.givenNameRita
person.givenNameSusana
person.identifier1333426
person.identifier1433605
person.identifier1022927
person.identifier184324
person.identifier.ciencia-id761C-044C-995B
person.identifier.ciencia-id5A17-09B5-48A5
person.identifier.ciencia-idD416-CB5B-AC3D
person.identifier.ciencia-id9F13-D310-B5A3
person.identifier.ciencia-id321C-EBE3-FBB2
person.identifier.orcid0000-0002-1613-7023
person.identifier.orcid0000-0002-6472-5700
person.identifier.orcid0000-0001-6923-8744
person.identifier.orcid0000-0001-5192-3006
person.identifier.orcid0000-0003-2603-4164
person.identifier.ridE-6798-2012
person.identifier.ridL-2649-2016
person.identifier.ridC-8012-2011
person.identifier.ridC-3062-2012
person.identifier.ridO-8297-2015
person.identifier.scopus-author-id7003891380
person.identifier.scopus-author-id8791713500
person.identifier.scopus-author-id57221975472
person.identifier.scopus-author-id8853708300
person.identifier.scopus-author-id36935590500
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication848d1c90-2438-4caa-b798-3f50305643d7
relation.isAuthorOfPublication331ff36d-5a01-45fe-a70f-52aaecf15554
relation.isAuthorOfPublication3466459e-d41d-436c-9b36-7e73e9d9cc9a
relation.isAuthorOfPublicationd6907c0a-3f8f-431c-acf2-0b257692f0d4
relation.isAuthorOfPublication08edcb2b-a4ab-4489-8b33-55c882265fe4
relation.isAuthorOfPublication.latestForDiscovery848d1c90-2438-4caa-b798-3f50305643d7
relation.isProjectOfPublication41fa1ccf-a3bf-4975-9bac-b2dbc9ad2f80
relation.isProjectOfPublication50d4c130-4418-49ce-80df-5b70324da5d6
relation.isProjectOfPublication718254be-c925-40e1-befc-ef8ab5913a8e
relation.isProjectOfPublicationd65aa48f-c597-4431-b836-3b77c40ee6a5
relation.isProjectOfPublication709b3685-d32e-4d8a-96e0-36042fb2e28a
relation.isProjectOfPublication.latestForDiscovery50d4c130-4418-49ce-80df-5b70324da5d6

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Proactive_RPacheco_ADEQ.pdf
Size:
1.49 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

ISEL - Eng. Quim. Biol. - Artigos