Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies

The first semisynthesis and biological profiling of the new abietane diterpenoid (+)-liquiditerpenoic acid A (abietopinoic acid) (7) along with several analogues are reported. The compounds were obtained from readily available methyl dehydroabietate (8), which was derived from (−)-abietic acid (1)....

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Autores: Hamulic, Damir, Stadler, Marco, Hering, Steffen, Padrón, José M., Bassett, Rachel, Rivas, Fátima, Loza-Mejía, Marco A., Dea-Ayuela, M. Auxiliadora, González-Cardenete, Miguel A.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/179190
Acceso en línea:http://hdl.handle.net/10261/179190
Access Level:acceso abierto
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spelling Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR StudiesHamulic, DamirStadler, MarcoHering, SteffenPadrón, José M.Bassett, RachelRivas, FátimaLoza-Mejía, Marco A.Dea-Ayuela, M. AuxiliadoraGonzález-Cardenete, Miguel A.The first semisynthesis and biological profiling of the new abietane diterpenoid (+)-liquiditerpenoic acid A (abietopinoic acid) (7) along with several analogues are reported. The compounds were obtained from readily available methyl dehydroabietate (8), which was derived from (−)-abietic acid (1). Biological comparison was conducted according to the different functional groups, leading to some basic structure–activity relationships (SAR). In particular, the ferruginol and sugiol analogues 7 and 10–16 were characterized by the presence of an acetylated phenolic moiety, an oxidized C-7 as a carbonyl, and a different functional group at C-18 (methoxycarbonyl, carboxylic acid, and hydroxymethyl). The biological properties of these compounds were investigated against a panel of six representative human tumor solid cells (A549, HBL-100, HeLa, SW1573, T-47D, and WiDr), five leukemia cellular models (NALM-06, KOPN-8, SUP-B15, UoCB1, and BCR-ABL), and four Leishmania species (L. infantum, L. donovani, L. amazonensis, and L. guyanensis). A molecular docking study pointed out some targets in these Leishmania species. In addition, the ability of the compounds to modulate GABAA receptors (α1β2γ2s) is also reported. The combined findings indicate that these abietane diterpenoids offer a source of novel bioactive molecules with promising pharmacological properties from cheap chiral-pool building blocks.Financial support by the Spanish Government [Consejo Superior de Investigaciones Científicas (201680I008)] is gratefully acknowledged. M.S. thanks the support by the doctoral program “Molecular Drug Targets” (Austrian Science Fund FWF W 1232). F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC). M.A.D.-A. thanks the Santander Bank for the support for her project in consolidable groups of CEU-UCH.Peer reviewedAmerican Chemical SocietyConsejo Superior de Investigaciones Científicas (España)Ministerio de Economía y Competitividad (España)Austrian Science FundBanco SantanderAmerican Lebanese Syrian Associated CharitiesGonzález-Cardenete, Miguel A. [0000-0002-8762-0426]Stadler, Marco [0000-0003-4489-6382]Padrón, José M. [0000-0002-7488-1774]Rivas, Fátima [0000-0003-3643-2035]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/179190reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1021/acs.jnatprod.8b00884Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1791902026-05-22T06:33:51Z
dc.title.none.fl_str_mv Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies
title Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies
spellingShingle Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies
Hamulic, Damir
title_short Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies
title_full Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies
title_fullStr Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies
title_full_unstemmed Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies
title_sort Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies
dc.creator.none.fl_str_mv Hamulic, Damir
Stadler, Marco
Hering, Steffen
Padrón, José M.
Bassett, Rachel
Rivas, Fátima
Loza-Mejía, Marco A.
Dea-Ayuela, M. Auxiliadora
González-Cardenete, Miguel A.
author Hamulic, Damir
author_facet Hamulic, Damir
Stadler, Marco
Hering, Steffen
Padrón, José M.
Bassett, Rachel
Rivas, Fátima
Loza-Mejía, Marco A.
Dea-Ayuela, M. Auxiliadora
González-Cardenete, Miguel A.
author_role author
author2 Stadler, Marco
Hering, Steffen
Padrón, José M.
Bassett, Rachel
Rivas, Fátima
Loza-Mejía, Marco A.
Dea-Ayuela, M. Auxiliadora
González-Cardenete, Miguel A.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas (España)
Ministerio de Economía y Competitividad (España)
Austrian Science Fund
Banco Santander
American Lebanese Syrian Associated Charities
González-Cardenete, Miguel A. [0000-0002-8762-0426]
Stadler, Marco [0000-0003-4489-6382]
Padrón, José M. [0000-0002-7488-1774]
Rivas, Fátima [0000-0003-3643-2035]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description The first semisynthesis and biological profiling of the new abietane diterpenoid (+)-liquiditerpenoic acid A (abietopinoic acid) (7) along with several analogues are reported. The compounds were obtained from readily available methyl dehydroabietate (8), which was derived from (−)-abietic acid (1). Biological comparison was conducted according to the different functional groups, leading to some basic structure–activity relationships (SAR). In particular, the ferruginol and sugiol analogues 7 and 10–16 were characterized by the presence of an acetylated phenolic moiety, an oxidized C-7 as a carbonyl, and a different functional group at C-18 (methoxycarbonyl, carboxylic acid, and hydroxymethyl). The biological properties of these compounds were investigated against a panel of six representative human tumor solid cells (A549, HBL-100, HeLa, SW1573, T-47D, and WiDr), five leukemia cellular models (NALM-06, KOPN-8, SUP-B15, UoCB1, and BCR-ABL), and four Leishmania species (L. infantum, L. donovani, L. amazonensis, and L. guyanensis). A molecular docking study pointed out some targets in these Leishmania species. In addition, the ability of the compounds to modulate GABAA receptors (α1β2γ2s) is also reported. The combined findings indicate that these abietane diterpenoids offer a source of novel bioactive molecules with promising pharmacological properties from cheap chiral-pool building blocks.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/179190
url http://hdl.handle.net/10261/179190
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1021/acs.jnatprod.8b00884
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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