Publication
Structure–Activity Relationship of Piplartine and Synthetic Analogues against Schistosoma mansoni and Cytotoxicity to Mammalian Cells
dc.contributor.author | Campelo, Yuri | |
dc.contributor.author | Ombredane, Alicia | |
dc.contributor.author | Vasconcelos, Andreanne | |
dc.contributor.author | Albuquerque, Lucas | |
dc.contributor.author | Moreira, Daniel | |
dc.contributor.author | Plácido, Alexandra | |
dc.contributor.author | Rocha, Jefferson | |
dc.contributor.author | Fokoue, Harold Hilarion | |
dc.contributor.author | Yamaguchi, Lydia | |
dc.contributor.author | Mafud, Ana | |
dc.contributor.author | Mascarenhas, Yvonne | |
dc.contributor.author | Delerue-Matos, Cristina | |
dc.contributor.author | Borges, Tatiana | |
dc.contributor.author | Joanitti, Graziella | |
dc.contributor.author | Arcanjo, Daniel | |
dc.contributor.author | Kato, Massuo | |
dc.contributor.author | Kuckelhaus, Selma | |
dc.contributor.author | Silva, Marcos | |
dc.contributor.author | Moraes, Josué | |
dc.contributor.author | Leite, José | |
dc.date.accessioned | 2019-09-13T09:45:41Z | |
dc.date.available | 2019-09-13T09:45:41Z | |
dc.date.issued | 2018-06 | |
dc.description.abstract | Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is an infectious disease mainly associated with poverty that affects millions of people worldwide. Since treatment for this disease relies only on the use of praziquantel, there is an urgent need to identify new antischistosomal drugs. Piplartine is an amide alkaloid found in several Piper species (Piperaceae) that exhibits antischistosomal properties. The aim of this study was to evaluate the structure–function relationship between piplartine and its five synthetic analogues (19A, 1G, 1M, 14B and 6B) against Schistosoma mansoni adult worms, as well as its cytotoxicity to mammalian cells using murine fibroblast (NIH-3T3) and BALB/cN macrophage (J774A.1) cell lines. In addition, density functional theory calculations and in silico analysis were used to predict physicochemical and toxicity parameters. Bioassays revealed that piplartine is active against S. mansoni at low concentrations (5⁻10 µM), but its analogues did not. In contrast, based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, piplartine exhibited toxicity in mammalian cells at 785 µM, while its analogues 19A and 6B did not reduce cell viability at the same concentrations. This study demonstrated that piplartine analogues showed less activity against S. mansoni but presented lower toxicity than piplartine. | pt_PT |
dc.description.sponsorship | This work was partially supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grant number 2016/22488-3), the authors are grateful to CAPES/FAPEPI for the scholarship granted. ACM is grateful to FAPESP (2014/02282-6). YPM is grateful to CNPq (Grant 302674/2010-1). Financial Support: FCT (Fundação para Ciência e Tecnologia) by grant no. UID/MULTI/04378/2013 POCI/01/0145/FEDER/007728, Fapesp (2014/50316-7). The work at UCIBIO/Requimte was supported by the Fundação para a Ciência e a Tecnologia (FCT) with financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT2020. Alexandra Plácido is grateful to FCT by her grant SFRH/BD/97995/2013, financed by POPH–QREN–Tipologia 4.1–Formação Avançada, subsidized by Fundo Social Europeu and Ministério da Ciência, Tecnologia e Ensino Superior. | pt_PT |
dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
dc.identifier.doi | 10.3390/ijms19061802 | |
dc.identifier.uri | http://hdl.handle.net/10400.22/14597 | |
dc.language.iso | eng | pt_PT |
dc.peerreviewed | yes | pt_PT |
dc.publisher | MDPI | pt_PT |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/19/6/1802 | pt_PT |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
dc.subject | 3T3 Cells | pt_PT |
dc.subject | Animals | pt_PT |
dc.subject | Anthelmintics | pt_PT |
dc.subject | Cricetinae | pt_PT |
dc.subject | Fibroblasts | pt_PT |
dc.subject | Macrophages | pt_PT |
dc.subject | Mice | pt_PT |
dc.subject | Mice, Inbred BALB C | pt_PT |
dc.subject | Piper | pt_PT |
dc.subject | Piperidones | pt_PT |
dc.subject | Plant Extracts | pt_PT |
dc.subject | Quantitative Structure-Activity Relationship | pt_PT |
dc.subject | Schistosoma mansoni | pt_PT |
dc.subject | Snails | pt_PT |
dc.title | Structure–Activity Relationship of Piplartine and Synthetic Analogues against Schistosoma mansoni and Cytotoxicity to Mammalian Cells | pt_PT |
dc.type | journal article | |
dspace.entity.type | Publication | |
oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04378%2F2013/PT | |
oaire.awardURI | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F97995%2F2013/PT | |
oaire.citation.issue | 6 | pt_PT |
oaire.citation.startPage | 1802 | pt_PT |
oaire.citation.title | International Journal of Molecular Sciences | pt_PT |
oaire.citation.volume | 19 | pt_PT |
oaire.fundingStream | 5876 | |
oaire.fundingStream | SFRH | |
person.familyName | Plácido | |
person.familyName | Delerue-Matos | |
person.givenName | Alexandra | |
person.givenName | Cristina | |
person.identifier | 1621053 | |
person.identifier.ciencia-id | 1B1A-461B-E8DD | |
person.identifier.ciencia-id | 9A1A-43FB-5C27 | |
person.identifier.orcid | 0000-0003-2706-7777 | |
person.identifier.orcid | 0000-0002-3924-776X | |
person.identifier.rid | L-3085-2014 | |
person.identifier.rid | D-4990-2013 | |
person.identifier.scopus-author-id | 55232677900 | |
person.identifier.scopus-author-id | 6603741848 | |
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 | |
rcaap.rights | openAccess | pt_PT |
rcaap.type | article | pt_PT |
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