Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells

ABSTRACT: Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. F...

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Autores:
Berrío Escobar, Jhon Fernando
Pastrana Restrepo, Manuel Humberto
Galeano Jaramillo, Elkin de Jesús
Márquez Fernández, Diana Margarita
Márquez Fernández, María Elena
Martínez Martínez, Alejandro
Tipo de recurso:
Article of investigation
Fecha de publicación:
2017
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/24051
Acceso en línea:
http://hdl.handle.net/10495/24051
http://revistaseug.ugr.es/index.php/ars/article/view/6441
Palabra clave:
Neoplasias de la Mama
Breast Neoplasms
Nucleósidos
Nucleosides
Uridina
Uridine
Citarabina
Cytarabine
Citotoxicidad
Cytotoxicity
http://aims.fao.org/aos/agrovoc/c_34251
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-sa/2.5/co/
id UDEA2_6f7d9a79f35cb9e73deb09548d2139e9
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/24051
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
dc.title.alternative.spa.fl_str_mv Síntesis y evaluación citotóxica de derivados halogenados y peracetylados de nucleósidos en células de cáncer de mama
title Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
spellingShingle Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
Neoplasias de la Mama
Breast Neoplasms
Nucleósidos
Nucleosides
Uridina
Uridine
Citarabina
Cytarabine
Citotoxicidad
Cytotoxicity
http://aims.fao.org/aos/agrovoc/c_34251
title_short Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
title_full Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
title_fullStr Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
title_full_unstemmed Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
title_sort Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cells
dc.creator.fl_str_mv Berrío Escobar, Jhon Fernando
Pastrana Restrepo, Manuel Humberto
Galeano Jaramillo, Elkin de Jesús
Márquez Fernández, Diana Margarita
Márquez Fernández, María Elena
Martínez Martínez, Alejandro
dc.contributor.author.none.fl_str_mv Berrío Escobar, Jhon Fernando
Pastrana Restrepo, Manuel Humberto
Galeano Jaramillo, Elkin de Jesús
Márquez Fernández, Diana Margarita
Márquez Fernández, María Elena
Martínez Martínez, Alejandro
dc.subject.decs.none.fl_str_mv Neoplasias de la Mama
Breast Neoplasms
Nucleósidos
Nucleosides
Uridina
Uridine
Citarabina
Cytarabine
topic Neoplasias de la Mama
Breast Neoplasms
Nucleósidos
Nucleosides
Uridina
Uridine
Citarabina
Cytarabine
Citotoxicidad
Cytotoxicity
http://aims.fao.org/aos/agrovoc/c_34251
dc.subject.agrovoc.none.fl_str_mv Citotoxicidad
Cytotoxicity
dc.subject.agrovocuri.none.fl_str_mv http://aims.fao.org/aos/agrovoc/c_34251
description ABSTRACT: Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. First, it was accomplished the halogenation reaction on the 5-position of the nitrogenous base, subsequently, the ester and amide derivatives were performed for all hydroxyl and amine group present in the nucleosides. Besides, the uridine acetonide derivatives as prepared by acid catalysis. The prod ucts were characterized by nuclear magnetic resonance spectroscopy (1H RMN y 13C RMN) and mass spectrometry in positive mode by direct injection. Derivatives were evaluated in Chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results. The four derivatives were obtained with chlorine and bromine for the uridine and cytarabine, respectively, their respective per-acetylated derivatives, the per-acetylated nucleoside and the uridine acetonide; the compounds were obtained with efficiency over 90%. The per-acetylated nucleosides and the halogenated and per-acetylated derivatives did not show inhibitory effects on cell viability in MCF-7 cell line. However, the per-acetylated and halo genated derivatives presented a higher cytotoxic activity than their respective per-acetylated nucleoside. The uridine 3’,4’-acetonide showed a significant cytotoxicity on both cell lines.Conclusions. The per-acetylated nucleoside, and the respective halogenated derivatives with chlorine and bromine were obtained with high yields, nevertheless, these compounds did not exhibit a significant anti-proliferative activity (p˂0.05), possibly due to a low intra-cellular activation.
publishDate 2017
dc.date.issued.none.fl_str_mv 2017
dc.date.accessioned.none.fl_str_mv 2021-11-13T00:04:08Z
dc.date.available.none.fl_str_mv 2021-11-13T00:04:08Z
dc.type.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.hasversion.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
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dc.type.local.spa.fl_str_mv Artículo de investigación
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status_str publishedVersion
dc.identifier.issn.none.fl_str_mv 0004-2927
2340-9894
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/10495/24051
dc.identifier.doi.none.fl_str_mv 10.4321/S2340-98942017000400001
dc.identifier.url.spa.fl_str_mv http://revistaseug.ugr.es/index.php/ars/article/view/6441
identifier_str_mv 0004-2927
2340-9894
10.4321/S2340-98942017000400001
url http://hdl.handle.net/10495/24051
http://revistaseug.ugr.es/index.php/ars/article/view/6441
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Ars Pharm.
dc.rights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-sa/2.5/co/
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eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/2.5/co/
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dc.format.extent.spa.fl_str_mv 10
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Universidad de Granada, Facultad de Farmacia
dc.publisher.group.spa.fl_str_mv Productos Naturales Marinos
dc.publisher.place.spa.fl_str_mv Granada, España
institution Universidad de Antioquia
bitstream.url.fl_str_mv http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/2/license_rdf
http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/3/license.txt
http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/1/BerrioJhon_2017_SynthesisCytotoxicActivityPer-acetylatedHalogenated.pdf
bitstream.checksum.fl_str_mv e2060682c9c70d4d30c83c51448f4eed
8a4605be74aa9ea9d79846c1fba20a33
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spelling Berrío Escobar, Jhon FernandoPastrana Restrepo, Manuel HumbertoGaleano Jaramillo, Elkin de JesúsMárquez Fernández, Diana MargaritaMárquez Fernández, María ElenaMartínez Martínez, Alejandro2021-11-13T00:04:08Z2021-11-13T00:04:08Z20170004-29272340-9894http://hdl.handle.net/10495/2405110.4321/S2340-98942017000400001http://revistaseug.ugr.es/index.php/ars/article/view/6441ABSTRACT: Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. First, it was accomplished the halogenation reaction on the 5-position of the nitrogenous base, subsequently, the ester and amide derivatives were performed for all hydroxyl and amine group present in the nucleosides. Besides, the uridine acetonide derivatives as prepared by acid catalysis. The prod ucts were characterized by nuclear magnetic resonance spectroscopy (1H RMN y 13C RMN) and mass spectrometry in positive mode by direct injection. Derivatives were evaluated in Chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results. The four derivatives were obtained with chlorine and bromine for the uridine and cytarabine, respectively, their respective per-acetylated derivatives, the per-acetylated nucleoside and the uridine acetonide; the compounds were obtained with efficiency over 90%. The per-acetylated nucleosides and the halogenated and per-acetylated derivatives did not show inhibitory effects on cell viability in MCF-7 cell line. However, the per-acetylated and halo genated derivatives presented a higher cytotoxic activity than their respective per-acetylated nucleoside. The uridine 3’,4’-acetonide showed a significant cytotoxicity on both cell lines.Conclusions. The per-acetylated nucleoside, and the respective halogenated derivatives with chlorine and bromine were obtained with high yields, nevertheless, these compounds did not exhibit a significant anti-proliferative activity (p˂0.05), possibly due to a low intra-cellular activation.RESUMEN: Objetivos: Sintetizar derivados halogenados sobre la base nitrogenada, sus respectivos derivados tipo éster o amida de todos los grupos hidroxilo y amina presentes en los nucleósidos uridina y citarabina, y evaluar su actividad citotóxica sobre una línea celular de cáncer de mama. Metodología: primero se realizó la reacción de halogenación en la posición 5 de la base nitrogenada, posteriormente se formaron los ésteres y amidas de todos los grupos hidroxilos y amino presentes en los nucleósidos. Además, se preparó el derivado acetónido con catálisis ácida. Los compuestos se caracterizaron por espectroscopía de resonancia magnética nuclear (RMN 1H y RMN 13C) y espectrometría de masas por inyección directa en modo positivo. Los derivados se evaluaron sobre líneas celulares de tumor de Ovario de Hámster Chino (CHO) y de cáncer de mamá (MCF-7). Resultados: Se obtuvieron 4 derivados mono-halogenados con cloro y bromo de la uridina y citarabina, respectivamente, sus respectivos derivados per-acetilados, los nucleósidos per-acetilados y el acetónido de la uridina; los compuestos se obtuvieron con rendimientos superiores a 90%. Los nucleósidos peracetilados, y los derivados per-acetilados y halogenados no exhibieron una inhibición significativa de la viabilidad celular en ambas líneas celulares, sin embargo, de estos, los derivados per-acetilados y halogenados presentaron mayor actividad citotóxica que los respectivos nucleósidos per-acetilados. El derivado acetónido de la uridina mostró citotoxicidad significativa sobre ambas líneas celulares. Conclusiones: se obtuvieron los nucleósidos per-acetilados y los respectivos derivados clorados y bromados de estos, con rendimientos altos, sin embargo, estos compuestos no exhibieron una actividad anti-proliferativa significativa (p˂0,05), posiblemente debido a una baja activación intra-celular de los nucleósidos.COL001504310application/pdfengUniversidad de Granada, Facultad de FarmaciaProductos Naturales MarinosGranada, Españainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by-nc-sa/4.0/Synthesis and cytotoxic activity of per-acetylated and halogenated derivatives of nucleosides in breast cancer cellsSíntesis y evaluación citotóxica de derivados halogenados y peracetylados de nucleósidos en células de cáncer de mamaNeoplasias de la MamaBreast NeoplasmsNucleósidosNucleosidesUridinaUridineCitarabinaCytarabineCitotoxicidadCytotoxicityhttp://aims.fao.org/aos/agrovoc/c_34251Ars Pharm.Ars Pharmaceutica145154584CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-81051http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/2/license_rdfe2060682c9c70d4d30c83c51448f4eedMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53ORIGINALBerrioJhon_2017_SynthesisCytotoxicActivityPer-acetylatedHalogenated.pdfBerrioJhon_2017_SynthesisCytotoxicActivityPer-acetylatedHalogenated.pdfArtículo de investigaciónapplication/pdf650592http://bibliotecadigital.udea.edu.co/bitstream/10495/24051/1/BerrioJhon_2017_SynthesisCytotoxicActivityPer-acetylatedHalogenated.pdf7d60df163dd1bf4df1ba490a33e7327bMD5110495/24051oai:bibliotecadigital.udea.edu.co:10495/240512021-11-12 19:23:58.006Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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