Details

Autor(en) / Beteiligte

• Lari, Matteo
• Martínez-Alonso, Marta
• Busto, Natalia
• Manzano, Blanca R
• Rodríguez, Ana M
• Acuña, M. Isabel
• Domínguez, Fernando
• Albasanz, José L
• Leal, José M
• Espino, Gustavo
• García, Begoña

Titel

Strong Influence of Ancillary Ligands Containing Benzothiazole or Benzimidazole Rings on Cytotoxicity and Photoactivation of Ru(II) Arene Complexes

Ist Teil von

• Inorganic chemistry, 2018-11, Vol.57 (22), p.14322-14336

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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).