Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D

The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffo...

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Autores: Pla Queral, Daniel, Marchal, Antonio, Olsen, Christian A., Francesch, Andrés, Cuevas, Carmen, Albericio Palomera, Fernando, Álvarez Domingo, Mercedes
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2006
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/56314
Acceso en línea:https://hdl.handle.net/2445/56314
Access Level:acceso abierto
Palabra clave:Alcaloides
Productes naturals marins
Compostos heterocíclics
Medicaments antineoplàstics
Isoquinolina
Alkaloids
Marine natural products
Heterocyclic compounds
Antineoplastic agents
Isoquinoline
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oai_identifier_str oai:diposit.ub.edu:2445/56314
network_acronym_str ES
network_name_str España
repository_id_str
spelling Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin DPla Queral, DanielMarchal, AntonioOlsen, Christian A.Francesch, AndrésCuevas, CarmenAlbericio Palomera, FernandoÁlvarez Domingo, MercedesAlcaloidesProductes naturals marinsCompostos heterocíclicsMedicaments antineoplàsticsIsoquinolinaAlkaloidsMarine natural productsHeterocyclic compoundsAntineoplastic agentsIsoquinolineThe marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB- 231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data the SAR study concluded that more than 75% of the open-chain Lam-D analogs tested showed cytotoxicity in a low micromolar GI50 range.American Chemical Society2006info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/56314Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: http://dx.doi.org/10.1021/jm0602458Journal of Medicinal Chemistry, 2006, vol. 49, num. 11, p. 3257-3268http://dx.doi.org/10.1021/jm0602458(c) American Chemical Society , 2006info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/563142026-05-27T06:46:51Z
dc.title.none.fl_str_mv Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
title Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
spellingShingle Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
Pla Queral, Daniel
Alcaloides
Productes naturals marins
Compostos heterocíclics
Medicaments antineoplàstics
Isoquinolina
Alkaloids
Marine natural products
Heterocyclic compounds
Antineoplastic agents
Isoquinoline
title_short Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
title_full Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
title_fullStr Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
title_full_unstemmed Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
title_sort Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
dc.creator.none.fl_str_mv Pla Queral, Daniel
Marchal, Antonio
Olsen, Christian A.
Francesch, Andrés
Cuevas, Carmen
Albericio Palomera, Fernando
Álvarez Domingo, Mercedes
author Pla Queral, Daniel
author_facet Pla Queral, Daniel
Marchal, Antonio
Olsen, Christian A.
Francesch, Andrés
Cuevas, Carmen
Albericio Palomera, Fernando
Álvarez Domingo, Mercedes
author_role author
author2 Marchal, Antonio
Olsen, Christian A.
Francesch, Andrés
Cuevas, Carmen
Albericio Palomera, Fernando
Álvarez Domingo, Mercedes
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Alcaloides
Productes naturals marins
Compostos heterocíclics
Medicaments antineoplàstics
Isoquinolina
Alkaloids
Marine natural products
Heterocyclic compounds
Antineoplastic agents
Isoquinoline
topic Alcaloides
Productes naturals marins
Compostos heterocíclics
Medicaments antineoplàstics
Isoquinolina
Alkaloids
Marine natural products
Heterocyclic compounds
Antineoplastic agents
Isoquinoline
description The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB- 231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data the SAR study concluded that more than 75% of the open-chain Lam-D analogs tested showed cytotoxicity in a low micromolar GI50 range.
publishDate 2006
dc.date.none.fl_str_mv 2006
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/56314
url https://hdl.handle.net/2445/56314
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://dx.doi.org/10.1021/jm0602458
Journal of Medicinal Chemistry, 2006, vol. 49, num. 11, p. 3257-3268
http://dx.doi.org/10.1021/jm0602458
dc.rights.none.fl_str_mv (c) American Chemical Society , 2006
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Chemical Society , 2006
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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