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Strong Influence of Ancillary Ligands Containing Benzothiazole or Benzimidazole Rings on Cytotoxicity and Photoactivation of Ru(II) Arene Complexes.
- Source :
-
Inorganic chemistry [Inorg Chem] 2018 Nov 19; Vol. 57 (22), pp. 14322-14336. Date of Electronic Publication: 2018 Oct 31. - Publication Year :
- 2018
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Abstract
- A new family of neutral ruthenium(II) arene complexes of the type [Ru(η <superscript>6</superscript> -arene)X(κ <superscript>2</superscript> - O, N-L)] (η <superscript>6</superscript> -arene = p-cym, bz; X = Cl <superscript>-</superscript> , SCN <superscript>-</superscript> ; 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(η <superscript>6</superscript> - p-cym)(NCS)(κ <superscript>2</superscript> - 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(κ <superscript>2</superscript> - O, N-L2)(κ <superscript>1</superscript> - S-DMSO) <subscript>2</subscript> (μ-SCN)] <subscript>2</subscript> [3c] and [Ru(κ <superscript>2</superscript> - O, N-L2)(κ <superscript>1</superscript> - S-DMSO) <subscript>3</subscript> (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).
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Antineoplastic Agents radiation effects
Benzimidazoles chemical synthesis
Benzimidazoles chemistry
Benzimidazoles radiation effects
Benzothiazoles chemical synthesis
Benzothiazoles chemistry
Benzothiazoles radiation effects
Cattle
Cell Line, Tumor
Coordination Complexes chemical synthesis
Coordination Complexes chemistry
Coordination Complexes radiation effects
DNA chemistry
Fluorescence
Humans
Hydrogen-Ion Concentration
Intercalating Agents chemical synthesis
Intercalating Agents chemistry
Intercalating Agents pharmacology
Intercalating Agents radiation effects
Ligands
Molecular Structure
Photosensitizing Agents chemical synthesis
Photosensitizing Agents chemistry
Photosensitizing Agents radiation effects
Ultraviolet Rays
Antineoplastic Agents pharmacology
Benzimidazoles pharmacology
Benzothiazoles pharmacology
Coordination Complexes pharmacology
Photosensitizing Agents pharmacology
Ruthenium chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-510X
- Volume :
- 57
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Inorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30379535
- Full Text :
- https://doi.org/10.1021/acs.inorgchem.8b02299