Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands
New water soluble, enantiopure arene ruthenium compound SRuSN-(1R,4S)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a′) has been synthesized. The novel compound along with that previously described RRuRN-(1S,4R)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Alcalá (UAH) |
| Repositorio: | e_Buah Biblioteca Digital Universidad de Alcalá |
| Idioma: | inglés |
| OAI Identifier: | oai:ebuah.uah.es:10017/60452 |
| Acceso en línea: | http://hdl.handle.net/10017/60452 https://dx.doi.org/10.1016/j.jinorgbio.2018.02.018 |
| Access Level: | acceso abierto |
| Palabra clave: | Anticancer Antimetastatic Chiral Cytotoxicity DNA In vivo. Química Chemistry |
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Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligandsCueva Alique, Isabel de laSierra Tornero, SaraMuñoz Moreno, Laura|||0000-0002-2322-8986Pérez Redondo, Adrián|||0000-0002-0086-8825Bajo Chueca, Ana María|||0000-0002-4944-4222Marzo, IsabelGude Rodríguez, Lourdes|||0000-0002-0220-3755Cuenca Agreda, José Tomás|||0000-0001-5830-5833Royo Cantabrana, Eva|||0000-0003-3818-6448AnticancerAntimetastaticChiralCytotoxicityDNAIn vivo.QuímicaChemistryNew water soluble, enantiopure arene ruthenium compound SRuSN-(1R,4S)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a′) has been synthesized. The novel compound along with that previously described RRuRN-(1S,4R)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a′ was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC50 values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a′ induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a′ towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells.Ministerio de Economía y CompetitividadComunidad Autónoma de MadridUniversidad de Alcalá20182018-06-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/60452https://dx.doi.org/10.1016/j.jinorgbio.2018.02.018reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)InglésengMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available CTQ2014-58270-RComunidad de Madrid http://dx.doi.org/10.13039/100012818 Not available I3 ProgramUAH Not available CCG2015%2FEXP-082UAH Not available CCG2015%2FBIO-010UAH Not available CCG2016%2FEXP-044UAH Not available CCG2016%2FEXP-028open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-ShareAlike 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/604522026-06-18T11:13:07Z |
| dc.title.none.fl_str_mv |
Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands |
| title |
Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands |
| spellingShingle |
Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands Cueva Alique, Isabel de la Anticancer Antimetastatic Chiral Cytotoxicity DNA In vivo. Química Chemistry |
| title_short |
Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands |
| title_full |
Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands |
| title_fullStr |
Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands |
| title_full_unstemmed |
Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands |
| title_sort |
Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands |
| dc.creator.none.fl_str_mv |
Cueva Alique, Isabel de la Sierra Tornero, Sara Muñoz Moreno, Laura|||0000-0002-2322-8986 Pérez Redondo, Adrián|||0000-0002-0086-8825 Bajo Chueca, Ana María|||0000-0002-4944-4222 Marzo, Isabel Gude Rodríguez, Lourdes|||0000-0002-0220-3755 Cuenca Agreda, José Tomás|||0000-0001-5830-5833 Royo Cantabrana, Eva|||0000-0003-3818-6448 |
| author |
Cueva Alique, Isabel de la |
| author_facet |
Cueva Alique, Isabel de la Sierra Tornero, Sara Muñoz Moreno, Laura|||0000-0002-2322-8986 Pérez Redondo, Adrián|||0000-0002-0086-8825 Bajo Chueca, Ana María|||0000-0002-4944-4222 Marzo, Isabel Gude Rodríguez, Lourdes|||0000-0002-0220-3755 Cuenca Agreda, José Tomás|||0000-0001-5830-5833 Royo Cantabrana, Eva|||0000-0003-3818-6448 |
| author_role |
author |
| author2 |
Sierra Tornero, Sara Muñoz Moreno, Laura|||0000-0002-2322-8986 Pérez Redondo, Adrián|||0000-0002-0086-8825 Bajo Chueca, Ana María|||0000-0002-4944-4222 Marzo, Isabel Gude Rodríguez, Lourdes|||0000-0002-0220-3755 Cuenca Agreda, José Tomás|||0000-0001-5830-5833 Royo Cantabrana, Eva|||0000-0003-3818-6448 |
| author2_role |
author author author author author author author author |
| dc.subject.none.fl_str_mv |
Anticancer Antimetastatic Chiral Cytotoxicity DNA In vivo. Química Chemistry |
| topic |
Anticancer Antimetastatic Chiral Cytotoxicity DNA In vivo. Química Chemistry |
| description |
New water soluble, enantiopure arene ruthenium compound SRuSN-(1R,4S)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a′) has been synthesized. The novel compound along with that previously described RRuRN-(1S,4R)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a′ was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC50 values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a′ induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a′ towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2018-06-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 NA http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10017/60452 https://dx.doi.org/10.1016/j.jinorgbio.2018.02.018 |
| url |
http://hdl.handle.net/10017/60452 https://dx.doi.org/10.1016/j.jinorgbio.2018.02.018 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available CTQ2014-58270-R Comunidad de Madrid http://dx.doi.org/10.13039/100012818 Not available I3 Program UAH Not available CCG2015%2FEXP-082 UAH Not available CCG2015%2FBIO-010 UAH Not available CCG2016%2FEXP-044 UAH Not available CCG2016%2FEXP-028 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-ShareAlike 4.0 International http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-ShareAlike 4.0 International http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| eu_rights_str_mv |
openAccess |
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application/pdf |
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reponame:e_Buah Biblioteca Digital Universidad de Alcalá instname:Universidad de Alcalá (UAH) |
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Universidad de Alcalá (UAH) |
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e_Buah Biblioteca Digital Universidad de Alcalá |
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e_Buah Biblioteca Digital Universidad de Alcalá |
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