Strong Influence of Ancillary Ligands Containing Benzothiazole or Benzimidazole Rings on Cytotoxicity and Photoactivation of Ru(II) Arene Complexes
- Matteo LariMatteo LariDepartamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainMore by Matteo Lari,
- Marta Martínez-AlonsoMarta Martínez-AlonsoDepartamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainMore by Marta Martínez-Alonso,
- Natalia Busto*Natalia Busto*E-mail: [email protected]Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainMore by Natalia Busto,
- Blanca R. ManzanoBlanca R. ManzanoDepartamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias y Tecnologías Químicas, IRICA, Universidad de Castilla-La Mancha, 13071 Ciudad Real, SpainMore by Blanca R. Manzano,
- Ana M. RodríguezAna M. RodríguezDepartamento de Química Inorgánica, Orgánica y Bioquímica, Escuela Técnica Superior de Ingenieros Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real, SpainMore by Ana M. Rodríguez,
- M. Isabel AcuñaM. Isabel AcuñaCIMUS, Universidad de Santiago de Compostela, Avenida Barcelona s/n, 15782 Santiago de Compostela, SpainMore by M. Isabel Acuña,
- Fernando DomínguezFernando DomínguezCIMUS, Universidad de Santiago de Compostela, Avenida Barcelona s/n, 15782 Santiago de Compostela, SpainMore by Fernando Domínguez,
- José L. AlbasanzJosé L. AlbasanzDepartamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias y Tecnologías Químicas, IRICA, Universidad de Castilla-La Mancha, 13071 Ciudad Real, SpainMore by José L. Albasanz,
- José M. LealJosé M. LealDepartamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainMore by José M. Leal,
- Gustavo Espino*Gustavo Espino*E-mail: [email protected]Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainMore by Gustavo Espino, and
- Begoña García*Begoña García*E-mail: [email protected]Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainMore by Begoña García
Abstract
A new family of neutral ruthenium(II) arene complexes of the type [Ru(η6-arene)X(κ2-O,N-L)] (η6-arene = p-cym, bz; X = Cl–, SCN–; HL1 = 2-(2′-hydroxyphenyl)benzimidazole, HL2 = 2-(2′-hydroxyphenyl)benzothiazole) has been synthesized and characterized. The cytotoxic activity of the Ru(II) complexes was evaluated in several tumor cell lines (A549, HepG2 and SW480) both in the dark and after soft irradiation with UV and blue light. None of the complexes bearing benzimidazole (HL1) as a ligand displayed phototoxicity, whereas the complexes with a benzothiazole ligand (HL2) exhibited photoactivation; the sensitivity observed for UV was higher than for blue light irradiation. The interesting results displayed by HL2 and [Ru(η6-p-cym)(NCS)(κ2-O,N-L2)], [3a], in terms of photo cytotoxicity prompted us to analyze their interaction with DNA, both in the dark and under irradiation conditions, in an effort to shed some light on their mechanism of action. The results of this study revealed that HL2 interacts with DNA by groove binding, whereas [3a] interacts by a dual mode of binding, an external groove binding, and covalent binding of the metal center to the guanine moiety. Interestingly, both HL2 and [3a] display a clear preference for AT base pairs, and this causes fluorescence enhancement. Additionally, cleavage of the pUC18 plasmid DNA by the complex is observed upon irradiation. The study of the irradiated form demonstrates that the arene ligand is released to yield species such as [Ru(κ2-O,N-L2)(κ1-S-DMSO)2(μ-SCN)]2[3c] and [Ru(κ2-O,N-L2)(κ1-S-DMSO)3(SCN)] [3d]. Such photo dissociation occurs even in the absence of oxygen and leads to cytotoxicity enhancement, an effect attributed to the presence of [3d], thus revealing the potential of [3a] as a pro-drug for photoactivated anticancer chemotherapy (PACT).
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This article is cited by 1 publications.
- Sen-ichi Aizawa, Kohei Takizawa, Momoko Aitani. Mechanistic study on substitution reaction of a citrato( p -cymene)Ru( ii ) complex with sulfur-containing amino acids. RSC Advances 2019, 9 (43) , 25177-25183. https://doi.org/10.1039/C9RA05507J