Study of the biological activity of photoactive bipyridyl-Ru(II) complexes containing 1,3,5-triaza-7-phosphaadamantane (PTA).

Autor: Del Pino JMV; Área de Química Inorgánica-CIESOL, Universidad de Almería, Almería, Spain., Scalambra F; Área de Química Inorgánica-CIESOL, Universidad de Almería, Almería, Spain., Bermejo-Casadesús C; Departament de Biologia, Universitat de Girona, Girona, Spain., Massaguer A; Departament de Biologia, Universitat de Girona, Girona, Spain., García-Maroto F; Área de BioQuímica, Universidad de Almería, Almería, Spain., Romerosa A; Área de Química Inorgánica-CIESOL, Universidad de Almería, Almería, Spain. Electronic address: romerosa@ual.es.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2023 Sep; Vol. 246, pp. 112291. Date of Electronic Publication: 2023 Jun 14.
DOI: 10.1016/j.jinorgbio.2023.112291
Abstrakt: The water-soluble ruthenium complex cis-[Ru(dcbpyH) 2 (PTAH) 2 ]Cl 2 ·3H 2 O (1) (dcbpy = 4,4'-dicarboxy-2,2'-bipyridine; PTA = 1,3,5-triaza-7-phosphaadamantane) has been synthesized and characterised by NMR, IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. The optical properties of 1 were studied, including photoactivation under visible light, as well as its biological properties, together with those of the previously published Ru complexes cis-[Ru(bpy) 2 (PTA) 2 ]Cl 2 (2), trans-[Ru(bpy) 2 (PTA) 2 ](CF 3 SO 3 ) 2 (3) and cis-[Ru(bpy) 2 (H 2 O)(PTA)](CF 3 SO 3 ) 2 (4) (bpy = 2,2'-bipyridine). Anticancer activities of the complexes against human lung (A549), cervical (HeLa) and prostate (PC3) carcinoma cells were evaluated under dark conditions and upon photoactivation with visible light. None of the complexes exhibited cytotoxic activity in the absence of light irradiation (IC 50  > 100 μM). However, after photoactivation, the cytotoxicity of complexes 1, 2 and 3 against the three cell lines markedly increased, resulting in IC 50 values between 25.3 μM and 9.3 μM. Notably, these complexes did not show toxicity against red blood cells. These findings show the potential of complexes 1, 2 and, particularly, 3 for selective and controlled cancer photochemotherapy. The reactivity of the Ru complexes against DNA under UV-Vis irradiation was studied by analysing plasmid mobility. Experimental data shows that 4 unfolds supercoiled DNA (SC DNA) both in the dark and under visible irradiation, while 1 and 3 are only active under light, being 2 inactive in either case. The unfolding activities of complexes 3 and 4 were dependent on the air present in the reaction. The measured intracellular levels of reactive oxygen species (ROS) upon irradiation with complexes 1, 2 and 3 suggest that their mechanism of action is related to oxidative stress.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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