Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives

[EN] The semisynthesis and biological activity of the naturally occurring abietane diterpenoids callitrisic acid (4a; 4-epidehydroabietic acid) and callitrisinol (6) are reported. These compounds and jiadifenoic acid C (5) were obtained from methyl callitrisate (4b) isolated from Sandarac resin for...

ver descrição completa

Detalhes bibliográficos
Autores: Stadler, Marco, Padron, Jose M., González-Cardenete, Miguel A
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/108063
Acesso em linha:https://riunet.upv.es/handle/10251/108063
Access Level:acceso abierto
Palavra-chave:Abietane diterpenes
Jiadifenoic acid
Callitrisic acid
Antiproliferative
GABAA receptor modulators
id ES_d15be1c2bfacb589db0e9bdfebc55a33
oai_identifier_str oai:riunet.upv.es:10251/108063
network_acronym_str ES
network_name_str España
repository_id_str
spelling Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid DerivativesStadler, MarcoPadron, Jose M.González-Cardenete, Miguel AAbietane diterpenesJiadifenoic acidCallitrisic acidAntiproliferativeGABAA receptor modulators[EN] The semisynthesis and biological activity of the naturally occurring abietane diterpenoids callitrisic acid (4a; 4-epidehydroabietic acid) and callitrisinol (6) are reported. These compounds and jiadifenoic acid C (5) were obtained from methyl callitrisate (4b) isolated from Sandarac resin for biological evaluation and comparison with the biological activities of C4 epimers such as dehydroabietic acid (2a). In particular, the antiproliferative activity against a panel of six representative human solid tumor cell lines (A549, HBL-100, HeLa, SW1573, T- 47D, WiDr) and the effect on GABAA receptors (¿1ß2¿2s) were evaluated. The GI50 values were in the range of 3.4¿61 ¿M and the potentiation of IGABA was 269¿311 % at 100 ¿M. Callitrisinol (6) was found to be 6.7-fold more potent than the reference etoposide in the WiDr (colon) cancer cell line. The role of the stereogenic center at C4 for antiproliferative and GABAA receptor modulating activities in the dehydroabietane scaffold has thus been revealed.Financial support by the Spanish Government [Consejo Superior de Investigaciones Científicas (201680I008)] is gratefully acknowledged. M. S. thanks the doctoral program “Molecular Drug Targets” (Austrian Science Fund FWF W 1232) for support.ThiemeConsejo Superior de Investigaciones CientíficasAustrian Science FundRepositorio Institucional de la Universitat Politècnica de València Riunet20172017-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/108063reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengComisión Sectorial de Investigación Científica, Uruguay https://doi.org/10.13039/501100003339 2001680I008Austrian Science Fund https://doi.org/10.13039/501100002428 W 1232 Molecular Drug Targetsopen accesshttp://purl.org/coar/access_right/c_abf2Reconocimiento - No comercial - Sin obra derivada (by-nc-nd) http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:riunet.upv.es:10251/1080632026-06-13T07:49:27Z
dc.title.none.fl_str_mv Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives
title Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives
spellingShingle Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives
Stadler, Marco
Abietane diterpenes
Jiadifenoic acid
Callitrisic acid
Antiproliferative
GABAA receptor modulators
title_short Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives
title_full Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives
title_fullStr Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives
title_full_unstemmed Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives
title_sort Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives
dc.creator.none.fl_str_mv Stadler, Marco
Padron, Jose M.
González-Cardenete, Miguel A
author Stadler, Marco
author_facet Stadler, Marco
Padron, Jose M.
González-Cardenete, Miguel A
author_role author
author2 Padron, Jose M.
González-Cardenete, Miguel A
author2_role author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas
Austrian Science Fund
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Abietane diterpenes
Jiadifenoic acid
Callitrisic acid
Antiproliferative
GABAA receptor modulators
topic Abietane diterpenes
Jiadifenoic acid
Callitrisic acid
Antiproliferative
GABAA receptor modulators
description [EN] The semisynthesis and biological activity of the naturally occurring abietane diterpenoids callitrisic acid (4a; 4-epidehydroabietic acid) and callitrisinol (6) are reported. These compounds and jiadifenoic acid C (5) were obtained from methyl callitrisate (4b) isolated from Sandarac resin for biological evaluation and comparison with the biological activities of C4 epimers such as dehydroabietic acid (2a). In particular, the antiproliferative activity against a panel of six representative human solid tumor cell lines (A549, HBL-100, HeLa, SW1573, T- 47D, WiDr) and the effect on GABAA receptors (¿1ß2¿2s) were evaluated. The GI50 values were in the range of 3.4¿61 ¿M and the potentiation of IGABA was 269¿311 % at 100 ¿M. Callitrisinol (6) was found to be 6.7-fold more potent than the reference etoposide in the WiDr (colon) cancer cell line. The role of the stereogenic center at C4 for antiproliferative and GABAA receptor modulating activities in the dehydroabietane scaffold has thus been revealed.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://riunet.upv.es/handle/10251/108063
url https://riunet.upv.es/handle/10251/108063
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Comisión Sectorial de Investigación Científica, Uruguay https://doi.org/10.13039/501100003339 2001680I008
Austrian Science Fund https://doi.org/10.13039/501100002428 W 1232 Molecular Drug Targets
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento - No comercial - Sin obra derivada (by-nc-nd)
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento - No comercial - Sin obra derivada (by-nc-nd)
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Thieme
publisher.none.fl_str_mv Thieme
dc.source.none.fl_str_mv reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname:Universitat Politècnica de València (UPV)
instname_str Universitat Politècnica de València (UPV)
reponame_str RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
collection RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420255063834624
score 15,301603

Registos relacionados