The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors
Descripción del Articulo
Financial support was received from The Wellcome Trust Travel Awards 2000, 2002; TWAS 02-051; CONCYTEC: 2002-2003, 441-2004 and PUCP-DAI: 3054, 0198, 3414, and E-032.
| Autores: | , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de Publicación: | 2008 |
| Institución: | Consejo Nacional de Ciencia Tecnología e Innovación |
| Repositorio: | CONCYTEC-Institucional |
| Lenguaje: | inglés |
| OAI Identifier: | oai:repositorio.concytec.gob.pe:20.500.12390/945 |
| Enlace del recurso: | https://hdl.handle.net/20.500.12390/945 https://doi.org/10.1016/j.bmc.2008.05.074 |
| Nivel de acceso: | acceso abierto |
| Materia: | Trypanosomatid Trypanothione reductase Enzymatic inhibition |
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CONC_3a49478c4a85b39ecbad51a001fd7cd6 |
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oai:repositorio.concytec.gob.pe:20.500.12390/945 |
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CONC |
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CONCYTEC-Institucional |
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4689 |
| dc.title.none.fl_str_mv |
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors |
| title |
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors |
| spellingShingle |
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors Galarreta B.C. Trypanosomatid Trypanothione reductase Enzymatic inhibition |
| title_short |
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors |
| title_full |
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors |
| title_fullStr |
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors |
| title_full_unstemmed |
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors |
| title_sort |
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors |
| author |
Galarreta B.C. |
| author_facet |
Galarreta B.C. Sifuentes R. Carrillo A.K. Sanchez L. Amado M.d.R.I. Maruenda H. |
| author_role |
author |
| author2 |
Sifuentes R. Carrillo A.K. Sanchez L. Amado M.d.R.I. Maruenda H. |
| author2_role |
author author author author author |
| dc.contributor.author.fl_str_mv |
Galarreta B.C. Sifuentes R. Carrillo A.K. Sanchez L. Amado M.d.R.I. Maruenda H. |
| dc.subject.en.fl_str_mv |
Trypanosomatid Trypanothione reductase Enzymatic inhibition |
| topic |
Trypanosomatid Trypanothione reductase Enzymatic inhibition |
| description |
Financial support was received from The Wellcome Trust Travel Awards 2000, 2002; TWAS 02-051; CONCYTEC: 2002-2003, 441-2004 and PUCP-DAI: 3054, 0198, 3414, and E-032. |
| publishDate |
2008 |
| dc.date.accessioned.none.fl_str_mv |
2024-05-30T23:13:38Z |
| dc.date.available.none.fl_str_mv |
2024-05-30T23:13:38Z |
| dc.date.issued.fl_str_mv |
2008 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/20.500.12390/945 |
| dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1016/j.bmc.2008.05.074 |
| dc.identifier.scopus.none.fl_str_mv |
2-s2.0-47349130269 |
| url |
https://hdl.handle.net/20.500.12390/945 https://doi.org/10.1016/j.bmc.2008.05.074 |
| identifier_str_mv |
2-s2.0-47349130269 |
| dc.language.iso.none.fl_str_mv |
eng |
| language |
eng |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.en.fl_str_mv |
Elsevier Ltd |
| dc.source.none.fl_str_mv |
reponame:CONCYTEC-Institucional instname:Consejo Nacional de Ciencia Tecnología e Innovación instacron:CONCYTEC |
| instname_str |
Consejo Nacional de Ciencia Tecnología e Innovación |
| instacron_str |
CONCYTEC |
| institution |
CONCYTEC |
| reponame_str |
CONCYTEC-Institucional |
| collection |
CONCYTEC-Institucional |
| repository.name.fl_str_mv |
Repositorio Institucional CONCYTEC |
| repository.mail.fl_str_mv |
repositorio@concytec.gob.pe |
| _version_ |
1844882991793307648 |
| spelling |
Publicationrp02586600rp02587600rp02584600rp02477400rp02585600rp00916500Galarreta B.C.Sifuentes R.Carrillo A.K.Sanchez L.Amado M.d.R.I.Maruenda H.2024-05-30T23:13:38Z2024-05-30T23:13:38Z2008https://hdl.handle.net/20.500.12390/945https://doi.org/10.1016/j.bmc.2008.05.0742-s2.0-47349130269Financial support was received from The Wellcome Trust Travel Awards 2000, 2002; TWAS 02-051; CONCYTEC: 2002-2003, 441-2004 and PUCP-DAI: 3054, 0198, 3414, and E-032.Twenty-three heterocyclic compounds were evaluated for their potential as trypanothione reductase inhibitors. As a result, the harmaline, 10-thiaisoalloxazine, and aspidospermine frameworks were identified as the basis of inhibitors of Trypanosoma cruzi trypanothione reductase. Two new compounds showed moderately strong, linear competitive inhibition, namely N,N-dimethyl-N-[3-(7-methoxy-1- methyl-3,4-dihydro-9H-b-carbolin-9-yl)propyl]amine (15) and 1,3-bis[3-(dimethylamino)propyl]-1,5- dihydro-2H-pyrimido[4,5-b][1,4]benzothiazine-2,4(3H)-dione (21), with Ki values of 35.1 ± 3.5 lM and 26.9 ±1.9 lM, respectively. Aspidospermine (25) inhibited T. cruzi TryR with a Ki of 64.6 ± 6.2 lM. None of the compounds inhibited glutathione reductase. Their toxicity toward promastigotes of Leishmania amazonensis was assessed.Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica - ConcytecengElsevier Ltdinfo:eu-repo/semantics/openAccessTrypanosomatidTrypanothione reductaseEnzymatic inhibitionThe use of natural product scaffolds as leads in the search for trypanothione reductase inhibitorsinfo:eu-repo/semantics/articlereponame:CONCYTEC-Institucionalinstname:Consejo Nacional de Ciencia Tecnología e Innovacióninstacron:CONCYTEC#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#20.500.12390/945oai:repositorio.concytec.gob.pe:20.500.12390/9452025-09-23 15:54:30.409http://purl.org/coar/access_right/c_14cbinfo:eu-repo/semantics/closedAccessmetadata only accesshttps://repositorio.concytec.gob.peRepositorio Institucional CONCYTECrepositorio@concytec.gob.pe#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#<Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="7e2a4619-6e80-4f55-bc75-7d623f15c42d"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2008</PublicationDate> <DOI>https://doi.org/10.1016/j.bmc.2008.05.074</DOI> <SCP-Number>2-s2.0-47349130269</SCP-Number> <Authors> <Author> <DisplayName>Galarreta B.C.</DisplayName> <Person id="rp02586" /> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> <Author> <DisplayName>Sifuentes R.</DisplayName> <Person id="rp02587" /> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> <Author> <DisplayName>Carrillo A.K.</DisplayName> <Person id="rp02584" /> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> <Author> <DisplayName>Sanchez L.</DisplayName> <Person id="rp02477" /> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> <Author> <DisplayName>Amado M.d.R.I.</DisplayName> <Person id="rp02585" /> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> <Author> <DisplayName>Maruenda H.</DisplayName> <Person id="rp00916" /> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Elsevier Ltd</DisplayName> <OrgUnit /> </Publisher> </Publishers> <Keyword>Trypanosomatid</Keyword> <Keyword>Trypanothione reductase</Keyword> <Keyword>Enzymatic inhibition</Keyword> <Abstract>Twenty-three heterocyclic compounds were evaluated for their potential as trypanothione reductase inhibitors. As a result, the harmaline, 10-thiaisoalloxazine, and aspidospermine frameworks were identified as the basis of inhibitors of Trypanosoma cruzi trypanothione reductase. Two new compounds showed moderately strong, linear competitive inhibition, namely N,N-dimethyl-N-[3-(7-methoxy-1- methyl-3,4-dihydro-9H-b-carbolin-9-yl)propyl]amine (15) and 1,3-bis[3-(dimethylamino)propyl]-1,5- dihydro-2H-pyrimido[4,5-b][1,4]benzothiazine-2,4(3H)-dione (21), with Ki values of 35.1 ± 3.5 lM and 26.9 ±1.9 lM, respectively. Aspidospermine (25) inhibited T. cruzi TryR with a Ki of 64.6 ± 6.2 lM. None of the compounds inhibited glutathione reductase. Their toxicity toward promastigotes of Leishmania amazonensis was assessed.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication> -1 |
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13.877373 |
Nota importante:
La información contenida en este registro es de entera responsabilidad de la institución que gestiona el repositorio institucional donde esta contenido este documento o set de datos. El CONCYTEC no se hace responsable por los contenidos (publicaciones y/o datos) accesibles a través del Repositorio Nacional Digital de Ciencia, Tecnología e Innovación de Acceso Abierto (ALICIA).
La información contenida en este registro es de entera responsabilidad de la institución que gestiona el repositorio institucional donde esta contenido este documento o set de datos. El CONCYTEC no se hace responsable por los contenidos (publicaciones y/o datos) accesibles a través del Repositorio Nacional Digital de Ciencia, Tecnología e Innovación de Acceso Abierto (ALICIA).
