Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies

We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2–4) were obtained (45–92% yields) from the thermal reaction (PhCCPh exchange) of [Ru2Cp2(CO)(μ-CO){μ-η1:η3-C(Ph)═C(Ph)...

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Autores: Bresciani, Giulio, Boni, Serena, Funaioli, Tiziana, Zacchini, Stefano, Pampaloni, Guido, Busto Vázquez, Natalia, Biver, Tarita, Marchetti, Fabio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Burgos (UBU)
Repositorio:Repositorio Institucional de la Universidad de Burgos (RIUBU)
OAI Identifier:oai:riubu.ubu.es:10259/11370
Acceso en línea:https://hdl.handle.net/10259/11370
Access Level:acceso abierto
Palabra clave:Antineoplásicos
Compuestos organometálicos
Antineoplastic agents
Organometallic compounds
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spelling Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological StudiesBresciani, GiulioBoni, SerenaFunaioli, TizianaZacchini, StefanoPampaloni, GuidoBusto Vázquez, NataliaBiver, TaritaMarchetti, FabioAntineoplásicosCompuestos organometálicosAntineoplastic agentsOrganometallic compoundsWe report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2–4) were obtained (45–92% yields) from the thermal reaction (PhCCPh exchange) of [Ru2Cp2(CO)(μ-CO){μ-η1:η3-C(Ph)═C(Ph)C(═O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc), 3-C6H4(Asp), 2-naphthyl; Cp = η5-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. Protonation of 1–3 by HBF4 afforded the corresponding μ-alkenyl derivatives 5–7, in 40–86% yields. All products were characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry (1, 2, 5, 7) and single-crystal X-ray diffraction (5, 7) analyses were performed on representative compounds. Complexes 5–7 revealed a cytotoxic activity comparable to that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma), and ovarian (A2780) cancer cell lines, and 2, 5, 6, and 7 overcame cisplatin resistance in A2780cis cells. Complexes 2, 5, and 7 (but not the aspirin derivative 6) induced an increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus, CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 is ineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity for this nucleic acid. Complexes 5–7 can interact with the albumin protein with a thermodynamic signature dominated by hydrophobic interactions. Overall, we show that organometallic species based on the Ru2Cp2(CO)x scaffold (x = 2, 3) are active against cancer cells, with different incorporated fragments influencing the interactions with nucleic acids and the production of ROS.We gratefully acknowledge for financial support La Caixa Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia, Innovación y Universidades (RTI2018-102040-B-100), Consejería de Educación, Junta de Castilla y León, FEDER (BU305P18), and the University of Pisa (Fondi di Ateneo 2021 and Fondi di Ateneo 2022). This contribution is part of the work from COST Action CA18202, NECTAR − Network for Equilibria and Chemical Thermodynamics Advanced Research, supported by COST (European Cooperation in Science and Technology). CIRCMSB (Consorzio InterUniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici) is also acknowledged.American Chemical Society202620262023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/10259/11370reponame:Repositorio Institucional de la Universidad de Burgos (RIUBU)instname:Universidad de Burgos (UBU)InglésInorganic Chemistry. 2023, V. 62, n. 31, p. 12453–12467https://doi.org/10.1021/acs.inorgchem.3c01644Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riubu.ubu.es:10259/113702026-05-28T07:56:11Z
dc.title.none.fl_str_mv Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies
title Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies
spellingShingle Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies
Bresciani, Giulio
Antineoplásicos
Compuestos organometálicos
Antineoplastic agents
Organometallic compounds
title_short Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies
title_full Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies
title_fullStr Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies
title_full_unstemmed Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies
title_sort Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies
dc.creator.none.fl_str_mv Bresciani, Giulio
Boni, Serena
Funaioli, Tiziana
Zacchini, Stefano
Pampaloni, Guido
Busto Vázquez, Natalia
Biver, Tarita
Marchetti, Fabio
author Bresciani, Giulio
author_facet Bresciani, Giulio
Boni, Serena
Funaioli, Tiziana
Zacchini, Stefano
Pampaloni, Guido
Busto Vázquez, Natalia
Biver, Tarita
Marchetti, Fabio
author_role author
author2 Boni, Serena
Funaioli, Tiziana
Zacchini, Stefano
Pampaloni, Guido
Busto Vázquez, Natalia
Biver, Tarita
Marchetti, Fabio
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antineoplásicos
Compuestos organometálicos
Antineoplastic agents
Organometallic compounds
topic Antineoplásicos
Compuestos organometálicos
Antineoplastic agents
Organometallic compounds
description We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2–4) were obtained (45–92% yields) from the thermal reaction (PhCCPh exchange) of [Ru2Cp2(CO)(μ-CO){μ-η1:η3-C(Ph)═C(Ph)C(═O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc), 3-C6H4(Asp), 2-naphthyl; Cp = η5-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. Protonation of 1–3 by HBF4 afforded the corresponding μ-alkenyl derivatives 5–7, in 40–86% yields. All products were characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry (1, 2, 5, 7) and single-crystal X-ray diffraction (5, 7) analyses were performed on representative compounds. Complexes 5–7 revealed a cytotoxic activity comparable to that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma), and ovarian (A2780) cancer cell lines, and 2, 5, 6, and 7 overcame cisplatin resistance in A2780cis cells. Complexes 2, 5, and 7 (but not the aspirin derivative 6) induced an increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus, CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 is ineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity for this nucleic acid. Complexes 5–7 can interact with the albumin protein with a thermodynamic signature dominated by hydrophobic interactions. Overall, we show that organometallic species based on the Ru2Cp2(CO)x scaffold (x = 2, 3) are active against cancer cells, with different incorporated fragments influencing the interactions with nucleic acids and the production of ROS.
publishDate 2023
dc.date.none.fl_str_mv 2023
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/10259/11370
url https://hdl.handle.net/10259/11370
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Inorganic Chemistry. 2023, V. 62, n. 31, p. 12453–12467
https://doi.org/10.1021/acs.inorgchem.3c01644
dc.rights.none.fl_str_mv Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
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 reponame:Repositorio Institucional de la Universidad de Burgos (RIUBU)
instname:Universidad de Burgos (UBU)
instname_str Universidad de Burgos (UBU)
reponame_str Repositorio Institucional de la Universidad de Burgos (RIUBU)
collection Repositorio Institucional de la Universidad de Burgos (RIUBU)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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