Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://repositorio-aberto.up.pt/handle/10216/82119 |
Resumo: | Electrospray ionization-ion trap mass spectrometry (ESI-MS) of imidazolidin-4-one peptidomimetic derivatives of the antimalarial drug primaquine (PQ) is reported. These compounds contain the imidazolidin-4-one moiety either at the N- or the C-terminal Of a dipeptide backbone, thus respectively mimicking PQ-Amino Acid-Proline (PQAAPro) and PQProAA derivatives of PQ. Both the peptidomimetics and Precursors previously developed by us are promising drug candidates, as they were found to be active against rodent Plasmodium berghei malaria and pneumocystis carinii pneumonia. Collision-induced dissociation (CID) and tandem-mass spectra (MS) of the title compounds, and fragmentation pathways thereof, led to the following findings: (1) CID patterns present some parallelism with the reactivity towards hydrolysis previously found for the same or related compounds; (2) a positional shift of the imidazolidin-4-one ring is reflected on both degree and pathways of fragmentation, which makes tandem-MS a key tool for differentiation of imidazolidin-4-one isomers; (3) the major MS/MS fragmentation of PQProAA mimetics involves release Of a neutral diketopiperazine (DKP), in parallel to the "diketopiperazine pathway" described in tandem-MS studies of oligopeptides; (4) the relative abundance of a major fragment in tandem-MS spectra is inversely Correlated with the size of the N-terminal AA in PQProAA mimetics. Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the 8-aminoquinoline and, especially, the imidazolidin-4-one structural classes. (J Am Soc Mass spectrom 2008, 19, 1476-1490) (C) 2008 American Society for Mass Spectrometry |
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Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial PrimaquineQuímicaChemical sciencesElectrospray ionization-ion trap mass spectrometry (ESI-MS) of imidazolidin-4-one peptidomimetic derivatives of the antimalarial drug primaquine (PQ) is reported. These compounds contain the imidazolidin-4-one moiety either at the N- or the C-terminal Of a dipeptide backbone, thus respectively mimicking PQ-Amino Acid-Proline (PQAAPro) and PQProAA derivatives of PQ. Both the peptidomimetics and Precursors previously developed by us are promising drug candidates, as they were found to be active against rodent Plasmodium berghei malaria and pneumocystis carinii pneumonia. Collision-induced dissociation (CID) and tandem-mass spectra (MS) of the title compounds, and fragmentation pathways thereof, led to the following findings: (1) CID patterns present some parallelism with the reactivity towards hydrolysis previously found for the same or related compounds; (2) a positional shift of the imidazolidin-4-one ring is reflected on both degree and pathways of fragmentation, which makes tandem-MS a key tool for differentiation of imidazolidin-4-one isomers; (3) the major MS/MS fragmentation of PQProAA mimetics involves release Of a neutral diketopiperazine (DKP), in parallel to the "diketopiperazine pathway" described in tandem-MS studies of oligopeptides; (4) the relative abundance of a major fragment in tandem-MS spectra is inversely Correlated with the size of the N-terminal AA in PQProAA mimetics. Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the 8-aminoquinoline and, especially, the imidazolidin-4-one structural classes. (J Am Soc Mass spectrom 2008, 19, 1476-1490) (C) 2008 American Society for Mass Spectrometry20082008-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://repositorio-aberto.up.pt/handle/10216/82119eng1044-030510.1016/j.jasms.2008.06.019Nuno ValeJoana MatosRui MoreiraPaula Gomesinfo: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:RCAAP2023-11-29T15:03:15Zoai:repositorio-aberto.up.pt:10216/82119Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:14:33.063278Repositório 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 |
Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine |
title |
Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine |
spellingShingle |
Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine Nuno Vale Química Chemical sciences |
title_short |
Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine |
title_full |
Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine |
title_fullStr |
Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine |
title_full_unstemmed |
Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine |
title_sort |
Electrospray Ionization-Ion Trap Mass Spectrometry Study of PQAAPro and PQProAA Mimetic Derivatives of the Antimalarial Primaquine |
author |
Nuno Vale |
author_facet |
Nuno Vale Joana Matos Rui Moreira Paula Gomes |
author_role |
author |
author2 |
Joana Matos Rui Moreira Paula Gomes |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Nuno Vale Joana Matos Rui Moreira Paula Gomes |
dc.subject.por.fl_str_mv |
Química Chemical sciences |
topic |
Química Chemical sciences |
description |
Electrospray ionization-ion trap mass spectrometry (ESI-MS) of imidazolidin-4-one peptidomimetic derivatives of the antimalarial drug primaquine (PQ) is reported. These compounds contain the imidazolidin-4-one moiety either at the N- or the C-terminal Of a dipeptide backbone, thus respectively mimicking PQ-Amino Acid-Proline (PQAAPro) and PQProAA derivatives of PQ. Both the peptidomimetics and Precursors previously developed by us are promising drug candidates, as they were found to be active against rodent Plasmodium berghei malaria and pneumocystis carinii pneumonia. Collision-induced dissociation (CID) and tandem-mass spectra (MS) of the title compounds, and fragmentation pathways thereof, led to the following findings: (1) CID patterns present some parallelism with the reactivity towards hydrolysis previously found for the same or related compounds; (2) a positional shift of the imidazolidin-4-one ring is reflected on both degree and pathways of fragmentation, which makes tandem-MS a key tool for differentiation of imidazolidin-4-one isomers; (3) the major MS/MS fragmentation of PQProAA mimetics involves release Of a neutral diketopiperazine (DKP), in parallel to the "diketopiperazine pathway" described in tandem-MS studies of oligopeptides; (4) the relative abundance of a major fragment in tandem-MS spectra is inversely Correlated with the size of the N-terminal AA in PQProAA mimetics. Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the 8-aminoquinoline and, especially, the imidazolidin-4-one structural classes. (J Am Soc Mass spectrom 2008, 19, 1476-1490) (C) 2008 American Society for Mass Spectrometry |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008 2008-01-01T00:00:00Z |
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 |
https://repositorio-aberto.up.pt/handle/10216/82119 |
url |
https://repositorio-aberto.up.pt/handle/10216/82119 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1044-0305 10.1016/j.jasms.2008.06.019 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
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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 |
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